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Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. To learn more, Dasm1 knockout mice were constructed and employed to confirm that Dasm1 regulates dendrite arborization and spine formation in vivo. We performed a yeast two-hybrid screen using Dasm1, revealing MRCKß as a putative partner; additional lines of evidence confirmed this interaction and identified cytoplasmic proline-rich region (823-947 aa) of Dasm1 and MRCKß self-activated kinase domain (CC1, 410-744 aa) as necessary and sufficient for binding. Using co-immunoprecipitation assay, autophosphorylation assay, and BS3 cross-linking assay, we show that Dasm1 binding triggers a change in MRCKß's conformation and subsequent dimerization, resulting in autophosphorylation and activation. Activated MRCKß in turn phosphorylates a class 2 regulatory myosin light chain, which leads to enhanced actin rearrangement, causing the dendrite outgrowth and spine formation observed before. Removal of Dasm1 in mice leads to behavioral abnormalities. Together, these results reveal a crucial molecular pathway mediating cell surface and intracellular signaling communication to regulate actin dynamics and neuronal development in the mammalian brain.
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Actinas/metabolismo , Dendritos/metabolismo , Imunoglobulinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Espinhas Dendríticas/metabolismo , Imunoglobulinas/química , Camundongos , Proteínas do Tecido Nervoso/química , Ligação Proteica , Domínios ProteicosRESUMO
Chemotherapy still accounts for a large proportion of the treatments of tumors, but the drug resistance and side effects caused by long-term chemotherapy should not be underestimated. In this work, the drug combination strategy has been widely developed to overcome the side effects brought by the use of single drugs and improve the therapeutic effect. However, in clinical applications, the co-delivery of drugs is very difficult, and different in vivo kinetics due to different drug properties will lead to a decrease in efficacy. Thus, the design of novel antitumor therapeutic agents, including new platinum agents, represents an area in need of urgent attention. Our investigation implies a promising strategy for the design of a platinum prodrug to enhance the treatment of breast cancer. A dual-drug delivery nanoparticle was developed for enhanced treatment of breast cancer based on a two-into-one co-delivery strategy. Through the synergistic effect of released cisplatin hydrate and tolfenamic acid (COX-2 inhibitor) from the coordination prodrug, the tumor growth is significantly suppressed, and the survival time is greatly extended in breast tumor-bearing mice.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Nanopartículas/química , Platina/farmacologia , Pró-Fármacos/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Breast cancer is the most common type of cancer in women. About 12% of all women in the United States will be diagnosed with breast cancer over their lifetimes. At the same time, incidences of brain metastases (BMs) are increasing and represent an emerging health threat. However, there is no effective chemotherapy for breast cancer brain metastases (BCBMs), which is largely due to lack of efficient delivery of antitumor drugs or drug combinations to the brain. In this study, oleanolic acid (OA), a natural pentacyclic triterpenoid compound with excellent antitumor activity, was found to form nanoparticles (NPs) and efficiently penetrate the brain for BCBMs treatment. On the basis of these findings, we developed a synergistic combinatorial chemotherapeutic regimen by formulating paclitaxel (PTX) into OA NPs and demonstrated that the resulting PTX-OA NPs effectively inhibited primary breast cancer and BCBMs in mouse xenografts. Collectively, this study introduces a new direction to treat primary breast cancer and BCBMs through noninvasive combination chemotherapy.
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Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Nanopartículas/química , Ácido Oleanólico/farmacologia , Paclitaxel/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Camundongos NusRESUMO
BACKGROUND: To investigate the safety and optical quality of small-incision lenticule extraction (SMILE) combined with monovision, and patient satisfaction with the procedure. METHODS: The present study assessed a non-random case series involving 60 eyes of 30 patients (mean age 45.53 ± 3.20 years [range 41 to 52 years]) treated bilaterally using the VisuMax 500 system (Carl Zeiss Meditec, Jena, Germany) between January and July 2016. The target refraction was plano for the distance eye, and between - 0.5 and - 1.75 diopters (D) for the near eye. Visual acuity, refraction errors, ocular aberrations, and satisfaction questionnaire scores were calculated 1 year after surgery. RESULTS: All surgeries were uneventful, with a mean safety index of 1.03 and 1.04 in dominant and nondominant eyes, respectively. Binocular uncorrected distance visual acuity of all patients was ≥20/32, while binocular uncorrected near visual acuity was ≥20/40 1 year postoperatively. Higher-order aberration (0.45 ± 0.14, 0.51 ± 0.15 µm), spherical (0.18 ± 0.15, 0.21 ± 0.14 µm) and coma aberration (0.31 ± 0.16, 0.27 ± 0.17 µm) were identical between dominant and nondominant eyes after surgery. The overall satisfaction rate was 86.7% (26/30), with large contributions from age (OR = 1.76 95% CI: 1.03-2.53; P = 0.036). Binocular uncorrected distance visual acuity was related to preoperative spherical diopter (r = - 0.500; P = 0.005). CONCLUSIONS: Monovision appears to be a safe and effective option for myopia patients with presbyopia who are considering the SMILE procedure. Patients with younger age were more satisfied with the procedure.
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Satisfação do Paciente , Presbiopia/cirurgia , Procedimentos Cirúrgicos Refrativos/métodos , Visão Monocular/fisiologia , Adulto , Feminino , Humanos , Lasers de Excimer/uso terapêutico , Masculino , Pessoa de Meia-Idade , Presbiopia/fisiopatologia , Procedimentos Cirúrgicos Refrativos/efeitos adversos , Análise de Regressão , Visão Binocular/fisiologia , Acuidade VisualRESUMO
Many malignant tumors, including breast cancer, exhibit amplification and overexpression of cyclin-dependent kinase 4 and 6 (CDK4/6). Ribociclib, approved and used in clinical treatment, acts as a highly selective CDK4/6 inhibitor for ER+/HER2- breast cancer. By modifying ribociclib with the chelator DOTA, we designed and synthesized a novel CDK4/6-positive PET imaging agent, which was radiolabeled by 68Ga for radioactive tagging. The radiotracer demonstrates high radiochemical purity, excellent stability in vitro and in vivo, and favorable pharmacokinetic characteristics. Cell uptake experiments using MCF-7 cells indicate that an excess of ribociclib (RBB) can inhibit cellular uptake of 68Ga-DOTA-RBB. Imaging and biodistribution experiments in MCF-7 tumor-bearing nude mice show significant radioactive accumulation in the tumor. However, preadministration of excess ribociclib results in a substantial reduction in radioactive accumulation within the tumor. On the basis of our explorations, 68Ga-DOTA-RBB, as a targeted imaging agent for CDK4/6-positive tumors, holds significant potential application values.
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Bisphenols (BPs) and parabens (PBs) are of great concern for environmental pollution and human health because of their endocrine-disrupting effects and potential health hazards. Urinary biomonitoring of BPs and PBs can provide basic data for human internal exposure evaluation, which is a prerequisite for accurately assessing their health risks. In this study, we developed a new pretreatment procedure based on solid supported liquid-liquid extraction (SLE) for the simultaneous separation of ten BPs and five PBs in human urine, followed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In the instrumental analysis, the HPLC conditions and MS/MS parameters were comprehensively optimized. Accurate qualitative and quantitative determination of ten BPs and five PBs was achieved by introducing a ternary gradient elution system of water, methanol, and acetonitrile for LC separation. During sample pretreatment, the extraction solvent and elution volume were optimized. Specifically, urine samples were held at room temperature and centrifuged at 3000 r/min for 10 min. The supernatant (2 mL) was then transferred to a glass tube, and the pH was adjusted to 5.0 using HCl (0.5 mL; 0.1 mol/L) and NaAc-HAc buffer (1.5 mL). Thereafter, ß-glucuronidase-arylsulfatase (20 µL) and surrogate standard solutions (10 ng;13C12-BPS,13C12-BPAF,13C6-MeP, and 13C6-BuP) were added, and the mixture was incubated in a shaker bath in the dark at 37 â for 16 h. After incubation, the hydrolyzed sample (4 mL) was loaded onto an SLE cartridge and equilibrated for a minimum of 5 min to ensure the solution was completely absorbed by the packing material. Subsequently, the target chemicals were eluted with a mixed ethyl acetate/n-hexane solution (3â¶7, v/v; 15 mL). Separation of the targets was performed on a ZORBAX SB-C18 reversed-phase column (250 mm×4.6 mm, 5 µm) using an acetonitrile-methanol-water system as the mobile phase. The method was verified by spiking mixed urine samples at three levels (1, 5, and 50 µg/L), with the recoveries ranging from 84.3% to 119.8%. Except for bisphenols (BPS), whose matrix effect was calculated as -21.8%, the matrix effects of other analytes were lower than 20%, indicating low matrix interference. The linear ranges of the analytes varied from 0.1-500 µg/L to 1-500 µg/L, with correlation coefficients higher than 0.995. The method limits of quantification for target chemicals ranged from 0.03 to 0.30 µg/L, and the relative standard deviations of intra- and inter-day experiments were 1.4%-8.4% and 5.7%-14.6%, respectively, suggesting high stability and reproducibility. The method was successfully applied to the determination of ten BPs and five PBs in 10 urine samples from a general population. The concentrations of target chemicals in the human urine samples varied. Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and bisphenol A (BPA) were detected in all samples, with median mass concentrations of 1.10, 0.60, 0.21, and 0.55 µg/L, respectively. The detection rates of the other chemicals were less than 50%, which may be related to the production and use of specific chemicals, their bioavailability, and biological metabolism in humans.
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Extração Líquido-Líquido , Parabenos , Fenóis , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Humanos , Extração Líquido-Líquido/métodos , Fenóis/urina , Fenóis/análise , Parabenos/análise , Compostos Benzidrílicos/urina , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The application of exogenous growth-regulating substances is an effective technique to enhance plant stress tolerance. Here, a hydroponic experiment was conducted to investigate the effects of exogenous basal application of 0.1 mmol·L-1 spermidine (Spd) on both the physiology and molecular biology of ryegrass root systems under varying degrees (0, 5, and 10 mg·L-1) of cadmium (Cd) stress using ryegrass as the test plants. The results of physiological studies revealed that Cd stress significantly reduced the physiological functions of the ryegrass root system, whereas the addition of Spd effectively alleviated the negative effects caused by Cd. The most significant effect was on the root soluble protein content, which increased by 90.91% and 158.35% compared with 5 mg·L-1and 10 mg·L-1 Cd alone. Spd also inhibited the accumulation of oxidative stress products malondialdehyde (MDA) and hydrogen peroxide (H2O2) by increasing the ascorbic acid (ASA) and glutathione (GSH) content and peroxidase (POD) activity, whereas the effects on root activity and superoxide dismutase (SOD) activity were not significant. The results of molecular biology studies demonstrated that 10 mg·L-1 Cd stress caused differential expression of a large number of genes in ryegrass roots, and the number of differentially expressed genes, differential significance, and differential multiplicity were significantly reduced after the application of exogenous Spd. The most significant part of the GO enrichment analysis shifted from responding to organic cyclic compounds and aldehyde/ketone group transferase activity to responding to trivalent iron ions and 2'-deoxymugineic-acid 2'-dioxygenase activity. Single gene expression heat map analysis revealed that exogenous Spd upregulated the expression of genes encoding zinc-iron transporter protein and 2'-deoxymugineic-acid 2'-dioxygenase, which improved the uptake and utilization of iron by the root system. In conclusion, the application of certain concentrations of Spd could effectively regulate the response of ryegrass roots to Cd stress, enhance its tolerance physiology, and mitigate the toxic effects of Cd.
Assuntos
Dioxigenases , Lolium , Espermidina/farmacologia , Espermidina/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Lolium/genética , Lolium/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Perfilação da Expressão Gênica , Dioxigenases/metabolismo , Dioxigenases/farmacologia , FerroRESUMO
Advanced drinking water treatment process using nanofiltration (NF) membranes has gained attention recently because it removes many challenging constituents in contaminated surface waters, such as dissolved organics and heavy metals. However, much literature has reported high variations and uncertainties of NF membranes for removing nitrogen compounds in the contaminated water-ammonium (NH4+), nitrates (NO3-), and nitrites (NO2-). This study aimed to identify the ability of commercial NF membranes to remove NH4+, NO2-, and NO3- and clarify the mechanisms underlying their transport through NF membranes. This was examined by evaluating their rejection by three commercial NF membranes using artificial and actual river waters under various conditions (variable permeate flux, temperature, pH, and ionic strength). Ammonium commonly showed the highest removal among the three nitrogen compounds, followed by nitrites and nitrates. Interestingly, ammonium removal varied considerably from 6% to 86%, depending on the membrane type and operating conditions. The results indicated that the selected nitrogen compounds (NH4+, NO2-, and NO3-) could be highly rejected depending on the clearance between their hydrated radius and the membrane's pore walls. Further, the rejection of the lowest molecular-weight nitrogen compound (NH4+) could be higher than NO2- and NO3- due to its highest energy barrier and larger hydrated radius. This study suggests that compliance with the drinking water regulations of NH4+, NO2-, and NO3- can be reliably achieved by selecting appropriate membrane types and predicting the range of their removal under various feed water quality and operating conditions.
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Compostos de Amônio , Água Potável , Nitratos/análise , Nitritos/análise , Dióxido de Nitrogênio , Nitrogênio/análiseRESUMO
Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.
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COVID-19 , Ácidos Nucleicos , Humanos , Vacina BNT162 , COVID-19/terapia , Sistemas de Liberação de Medicamentos , Terapia GenéticaRESUMO
A novel nanocontainer, which could regulate the release of payloads, has been successfully fabricated by attaching zwitterionic sulfobetaine copolymer onto the mesoporous silica nanoparticles (MSNs). RAFT polymerization is employed to prepare the hybrid poly(2-(dimethylamino)ethyl methacrylate)-coated MSNs (MSN-PDMAEMA). Subsequently, the tertiary amine groups in PDMAEMA are quaternized with 1,3-propanesultone to get poly(DMAEMA-co-3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate)-coated MSNs [MSN-Poly(DMAEMA-co-DMAPS)]. The zwitterionic PDMAPS component endows the nanocarrier with biocompatibility, and the PDMAEMA component makes the copolymer shell temperature-responsive. Controlled release of loaded rhodamine B has been achieved in the saline solutions.
Assuntos
Betaína/análogos & derivados , Betaína/síntese química , Nanocápsulas/química , Ácidos Polimetacrílicos/síntese química , Dióxido de Silício/química , Betaína/química , Betaína/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Metacrilatos/química , Nanocápsulas/toxicidade , Nanocápsulas/ultraestrutura , Nylons/química , Polimerização , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/toxicidade , Rodaminas/química , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
The investigation of biomagnification of polycyclic aromatic hydrocarbons (PAHs) and endosulfan, an organochlorine pesticide (OCP) and a new persistent organic pollutant, has been limited in freshwater food chains. The objective of the present study was to investigate the levels with focus on the sources and biomagnification of PAHs and OCPs in fish from Taihu Lake, China. In 193 samples of 24 species investigated, the concentrations ranged from 289 to 9 500 ng/g lipid weight (lw) for PAHs, and from 121 to 904 ng/g lw for OCPs, indicating that the fish in the lake was moderately contaminated. The PAHs mainly originated from both unburned petroleum and combustion of fossil fuels, and the OCPs from aged residues. It was unlikely that most of the PAHs and OCPs were biodiluted through the food chain because their trophic magnification factors were higher than one nevertheless the P-values >0.05. Aldrin, dieldrin, p,p'-DDE, p,p'-DDD, and endosulfan sulfate were significantly biomagnified through the food chain.
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Monitoramento Ambiental , Peixes , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Animais , China , Endossulfano/análise , Cadeia Alimentar , LagosRESUMO
The levels and distribution of six polycyclic musks, three nitromusks and 15 polycyclic aromatic hydrocarbons (PAHs) were investigated in sludge collected from 19 municipal wastewater treatment plants (WWTPs) in six cities in Guangdong Province, China. PAHs were detected in all of the sludge samples, and the levels of the total 15 PAHs ranged from 177.2-4421.8 µg/kg dry weight (dw). Four polycyclic musks, 4-acetyl-1,1-dimethyl-6-tert-butylindan (ADBI), 6-acetyl-1,1,2,3,3,5-hexamethylindan (AHMI), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta (g) -2-benzopyran (HHCB) and 7-acetyl -1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro naphthalene (AHTN), were found in these samples. The total concentrations of polycyclic musks varied from 794.4-12960.3 µg/kg dw, with HHCB and AHTN being the main components. Of the three nitromusks, 2,6-dinitro-3-methoxy-4-tert- butyl - toluene (MA) was only found in one sludge sample at the limit of detection (LOD) level, while 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene (Musk xylene, MX) and 4-acetyl-1-tert-butyl-3,5-dimethyl-2,6-dinitrobenzene (Musk ketone, MK) were found at levels ranging from the LOD to 65.8 µg/kg dw and LOD to 172.7 µg/kg dw, respectively, in most of the sludge samples. The PAHs, polycyclic musks and nitro musks were also shown to have various distribution patterns, possibly due to their different wastewater sources and wastewater treatment technology.
Assuntos
Ácidos Graxos Monoinsaturados/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Esgotos/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Análise de Componente PrincipalRESUMO
Designing and developing nanomedicine based on the tumor microenvironment (TME) for effective cancer treatment is highly desirable. In this work, polyvinyl pyrrolidone (PVP) dispersed nanoscale metal-organic framework (NMOF) of Fe-TCPP (TCPP = tetrakis (4-carboxyphenyl) porphyrin) loaded with hypoxia-activable prodrug tirapazamine (TPZ) and coated by the cancer cell membrane (CM) is constructed (the formed nanocomposite denoted as PFTT@CM). Due to the functionalization with the homologous cancer cell membrane, PFTT@CM is camouflaged to evade the immune clearance and preferentially accumulates at the tumor site. Once internalized by cancer cells, PFTT@CM is activated by the TME through redox reaction and Fenton reaction between Fe3+ in nano-platform and endogenous glutathione (GSH) and hydrogen peroxide (H2O2) to promote GSH exhausting as well as â¢OH and O2 production, which triggers ferroptosis and dramatically enhances photodynamic therapy (PDT) efficacy. Subsequently, the PDT process mediated by TCPP and light would consume oxygen and aggravate tumor hypoxia to further activate the prodrug TPZ for cancer chemotherapy. As a consequence, the TME-driven PFTT@CM nano-platform not only demonstrated its TME modulation ability but also showed a sequential synergistic therapy, which eventually inhibited the cancer cell proliferation. This multimodal nano-platform is expected to shed light on the design of TME-activatable reaction to reinforce the synergistic therapeutic outcome and facilitate the development of effective cancer nanomedicine.
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Neoplasias da Mama , Ferroptose , Estruturas Metalorgânicas , Neoplasias , Fotoquimioterapia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Membrana Celular , Feminino , Humanos , Peróxido de Hidrogênio/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Increasing evidence indicates that alternative splicing of human glucocorticoid receptor (GR) transcripts is implicated in the development of glucocorticoid resistance but the underlying mechanism was not well known. Serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 play an important role in the spliceosome assembly. In this study, we analyzed the effects of different SR proteins and hnRNP A1 on the alternative splicing of GR pre-mRNA in HeLa and 293T cells using a minigene transfection assay. Our results revealed that only SRp40 could induce a GRalpha to GRbeta shift of pre-mRNA splicing in exon 9 in HeLa cells and this effect induced by SRp40 was further confirmed by small interfering RNA study. However, in 293T cells, SRp40 could not induce this shift. These results indicated that SRp40 may influence the alternative splicing of GR pre-mRNA to regulate the ratio of GRalpha to GRbeta, and this effect is cell-dependent.
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Processamento Alternativo/fisiologia , Éxons/genética , Proteínas Nucleares/metabolismo , Precursores de RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores de Glucocorticoides/genética , Processamento Alternativo/genética , Linhagem Celular , Primers do DNA/genética , Humanos , Precursores de RNA/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Processamento de Serina-Arginina , TransfecçãoRESUMO
Based on special relativity, the formation mechanism of characteristic X-ray has been studied, and the influence of rotational mass effect on X-ray spectrum has been given. A calculation formula of the X-ray wavelength based upon special relativity was derived. Error analysis was carried out systematically for the calculation values of characteristic wavelength, and the rules of relative error were obtained. It is shown that the values of the calculation are very close to the experimental values, and the effect of rotational mass effect on the characteristic wavelength becomes more evident as the atomic number increases. The result of the study has some reference meaning for the spectrum analysis of characteristic X-ray in application.
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OBJECTIVE: To assess and compare the accuracy and regularity and short-term change of corneal flap in different flap preparation styles. METHODS: Eighty eyes of 40 cases were treated with laser-assisted subepithelial keratectomy. One hundred and fifty-five eyes of 78 cases were treated with laser in situ keratomileusis with 90 microm microkeratome flap preparation and eighty-two eyes of 42 cases were treated with laser in situ keratomileusis with 100 microm femtosecond laser flap preparation. Anterior segment optical coherence tomography was used to assess the thickness of epithelial or stromal flaps created with M2 microkeratome or VisuMax femtosecond laser by the same investigator 1 hour, 1 day, 1 week, 1 month and 3 months postoperatively, respectively. The thickness of twenty-five measuring points across each flap in LASIK, which were 1.5 mm, 2.5 mm and 3.5 mm away from vertex of cornea on the horizontal, vertical, 45 degrees and 135 degrees meridian respectively and the vertex of cornea itself, was evaluated. The results were analyzed with t-test or ANOVA by SPSS software. RESULTS: The thickness of epithelial flaps was (57.91 + or - 6.76), (54.94 + or - 4.65), (54.96 + or - 2.70), (55.26 + or - 4.27) and (53.86 + or - 5.56) microm at 1 hour, 1 day, 1 week, 1 month and 3 months respectively, with statistical significant difference between 1 hour and the other time points (F = 20.25, P < 0.05). The average thickness of stromal flaps on the vertex of cornea in microkeratome group was (129.16 + or - 12.10) microm, while (112.69 + or - 5.12) microm in the femtosecond laser group, which means the accuracy of flap preparation with femtosecond laser is better than with microkeratome. The absolute difference between actual and average thickness was (13.16 + or - 4.78) and (5.26 + or - 1.21) microm in the microkeratome group and femtosecond laser group, which means the reproducibility of flap preparation with femtosecond laser is better than with microkeratome as well. Flap morphology showed the feature of thin central area and thick peripheral area in microkeratome flap and uniformity in femtosecond laser flap, which illustrated the better regularity of femtosecond laser flap preparation. CONCLUSIONS: Anterior segment optical coherence tomography is a safe, quick and reliable facility to examine and assess flap morphology. Our results showed the accuracy and regularity of femtosecond laser flap preparation outweighed microkeratome flap preparation.
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Transplante de Córnea , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Miopia/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Córnea/diagnóstico por imagem , Humanos , Lasers de Excimer , Miopia/diagnóstico por imagem , Radiografia , Tomografia de Coerência Óptica , Adulto JovemRESUMO
The principal objective of this study was to investigate the strengthened remediation effect and relevant mechanism of P. aeruginosa on ryegrass (Lolium multiflorum Lam.) for soil contaminated by Cu-Pb-Cd compound heavy metals. The results showed that the complex heavy metals' contamination had remarkable inhibiting effect on the growth of plants (P < 0.01), and the biomass of ryegrass's stem and leaves declined by 28.2%, while that of roots decreased by 34.7% after 45 days. The inoculation of P. aeruginosa promoted the growth of ryegrass in polluted soil, in which the biomass recovered to the same level of that in normal plant; the activity of both catalase and urease in the soil also increased strikingly (by 29.3% and 75.7%, respectively); the ratio of residual heavy metals in the soil decreased, while the acid extractable heavy metals increased notably. Therefore, the absorption and accumulation of ryegrass to the heavy metals in soil were improved to some extent; the bioconcentration factor of Cu, Pb, and Cd in ryegrass increased by 35.9%, 55.6%, and 283.5%, respectively. The exterior microorganism allowed the accumulation of Cu, Pb, and Cd in shoots of ryegrass increasing remarkably, while in roots, only the accumulation of Pb increased by 16.3%, and that of both Cu and Cd decreased. Besides, in the P. aeruginosa-inoculated system, the transfer factor of Cu and Cd in plants increased strikingly, while that of Pb decreased.
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Lolium , Metais Pesados/análise , Poluentes do Solo/análise , Biodegradação Ambiental , Cádmio/análise , Cobre , Chumbo , Pseudomonas aeruginosa , SoloRESUMO
Nowadays, cell membrane-targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane-targeted self-delivery theranostic chimeric peptide CMP-PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real-time therapeutic feedback. Self-assembled CMP-PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP-PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)-carboxyfluorescein (FAM) and 4-(dimethylaminoazo)-benzene-4-carboxylic acid (Dabcyl). More importantly, CMP-PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP-PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp-Glu-Val-Asp (DEVD) is subsequently cleaved by activated caspase-3 and activated caspase-7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase-3 in vitro and in vivo to feedback real-time PDT therapeutic efficacy. In general, a novel cell membrane-targeted self-delivery theranostic chimeric peptide offers new promise for effective imaging-guided PDT.
Assuntos
Membrana Celular/metabolismo , Nanopartículas/química , Peptídeos/química , Fármacos Fotossensibilizantes/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Feminino , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Humanos , Luz , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Peptídeos/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This study investigated the degradation of sulfadiazine in three soils and also determined its sorption and hydrolysis behaviors as well. At the spike concentration of 10 mg/kg, the half-lives for sulfadiazine in the aerobic nonsterile soils ranged from 12 days to 18 days. Sulfadiazine was more persistent in the anoxic soils with the half-lives ranging between 57 days and 237 days and soil microorganisms played little role in the dissipation process under anoxic conditions. The decline in sulfadiazine concentrations was also observed in the sterile soils under aerobic conditions. Hydrolysis could not explain this phenomena as hydrolysis of sulfadiazine was pH dependent. Sulfadiazine only hydrolyzed to a very limited degree at acidic pH. Increased sorption was observed for sulfadiazine in soil 1 (pH 4.3) when the contact time increased to 14 days, but no significant increase in sorption was found for soil 2 (pH 7.2) and soil 3 (pH 8.5).
Assuntos
Anti-Infecciosos/química , Solo/análise , Sulfadiazina/química , Adsorção , Hidrólise , Cinética , Oxigênio/química , Água/químicaRESUMO
Due to its many advantages, such as miniaturization, high accuracy, high resolution, fast scanning speed, increased robustness and good stability, acousto-optic tunable filter (AOTF)-near infrared (NIR) spectrometer has been successfully applied in many fields. However, up to now, the commercial AOTF-NIR spectrometers can only be used for liquid and solid detection, but not for the detection of gaseous samples. In the present paper, the feasibility of quantitative analysis of gaseous mixtures by using AOTF-NIR spectrometer was investigated. A homemade gas cell was assembled to an AOTF-NIR spectrometer with probe for liquid detection to obtain NIR spectra of detected gas samples. The gas samples were composed of two groups: single-component CH4 and ternary component gaseous mixture of CH4, C2 H6, and C3 H8. The detection ability of fitted AOTF-NIR spectrometer was tested firstly. Comparing the absorption spectra of various concentrations, the absorbance of CH4 in absorption bands obviously increased with concentration increasing when the concentration was over 0.1%. According to the detection results, the lower limit of detection (LLD) of the AOTF-NIR spectrometer with gas cell was estimated to be 898 microL x L(-1). Subsequently, the NIR spectra of ternary mixtures were collected. The kernel partial least squares (KPLS) regression was employed to create the quantitative analysis model of three components gases. To evaluate the analysis ability of KPLS model, the PLS model was also created. The prediction results of the identical testing set show that the root mean square error of prediction (RMSEP) of three components predicted by KPLS model was 1.08%, 0.87%, and 0.79%, respectively, less than the RMSEP by PLS model. The exploratory work indicates that accurate quantitative analysis of ternary component alkane gaseous mixtures can be achieved by fitted AOTF-NIR spectrometer despite of some limitations, and KPLS regression is an excellent approach to NIR spectra analysis.