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1.
Artigo em Inglês | MEDLINE | ID: mdl-32696557

RESUMO

Benzene hydrogenation is one of important industrial processes. The reaction is incomplete, resulting in a mixture of benzene, cyclohexane and/or cyclohexene which have to be separated before the following reactions. The currently-used extractive and azeotropic distillations are operationally complex and energy-intensive. Adsorptive separation provides an alternative energy-efficient method. However, the separation of the ternary mixture has not been reported with adsorptive separation. In the present research, we report two macrocyclic hosts with hydrogen bonding sites in their cavities, which are able to separate the ternary mixture of benzene, cyclohexene and cyclohexane. N-H⋅⋅⋅π interactions were found to play a key role in the selective separation. In addition, fast adsorption, high loading ratios and easy recycling are achieved with the present system, promising for practical applications.

2.
Int J Med Sci ; 17(12): 1692-1703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714072

RESUMO

Reconstruction of bone defects is one of the most substantial and difficult clinical challenges in orthopedics. Transforming growth factor beta 1 (TGFß1) might play an important role in stimulating osteogenic differentiation of bone morphogenetic protein 9 (BMP9)-induced C3H10T1/2 mesenchymal stem cells. In our current study, we examined the potential synergy between TGFß1 and BMP9 in promoting the osteogenesis of C3H10T1/2 cells, and whether such effects could contribute to bone formation in vivo. Our experiment data indicated that TGFß1 could increase the expression of osteogenic markers and the formation of mineralized calcium nodules in, while suppressing the proliferation of, BMP9-induced C3H10T1/2 cells. Furthermore, mice intramuscularly injected with BMP9/TGFß1-transduced C3H10T1/2 cells into the gastrocnemius muscle on their tibiae developed ectopic bone masses with more mature osteoid structures, compared to those grafted with cells expressing BMP9/RFP. Subsequent mechanistic studies found that TGFß1-induced enhancement of osteogenesis in BMP9-overexpressing C3H10T1/2 cells was accompanied by augmented expression of heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for collagen biosynthesis, and can be attenuated by pirfenidone, a known anti-fibrotic inhibitor. Interestingly, protein microarray analysis suggested that TGFß1/BMP9-dependent osteogenesis of C3H10T1/2 cells seemed to involve several non-canonical signaling pathways such as Janus kinase-signal transducer and activator of transcription, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase. These results provided further evidence that TGFß1 could promote bone formation from BMP9-induced C3H10T1/2 cells and shed important light on the underlying molecular mechanisms.

3.
Int J Biol Sci ; 16(12): 2063-2071, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549754

RESUMO

Krüppel-like factor 10 (KLF10) has been identified as an important regulator in carcinogenesis and cancer progression. However, the role of KLF10 in multiply myeloma (MM) development and progression remains unknown. In present study, we found that KLF10 mRNA and protein were down-regulated in MM tissues and cell lines. Notably, KLF10 inhibited cell proliferation, cell cycle progression and promoted apoptosis in vitro and in vivo. Furthermore, we confirmed that KLF10 inhibited ß-catenin nuclear translocation and inhibited PTTG1 transcription. PTTG1 knockdown could mimic the biological effects of KLF10. Moreover, we demonstrated that KLF10 expression was regulated by miR-106b-5p. In MM tissues, miR-106b-5p has an inverse correlation with KLF10 expression. Conclusively, our results demonstrated that KLF10 functions as a tumor suppressor in regulating tumor growth of MM under regulation of miR-106b-5p, supporting its potential therapeutic target for MM.

4.
Technol Health Care ; 28(S1): 433-442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32364176

RESUMO

BACKGROUND: A two-hospital patient referral problem intends to calculate an optimal value of referral patients between two hospitals and to evaluate whether or not the current number of referral patients is too low. OBJECTIVE: The goal of this study is to develop a simulation-based optimization algorithm to find the optimal referral between two hospitals with the unfixed daily patient referral policy. METHODS: This study applied system simulation and a bat algorithm (BA) to build a simulation model in accordance with the status of the two hospitals case and to calculate an optimal value of daily referral patients. RESULTS: Based on the 20 test instances, we verified the stability of this algorithm. The results show that the average magnetic resonance imaging (MRI) patient wait time reduced from 16 days to eight days. The hospital should increase the average total monthly MRI referral patients to 370 under the limitation of the daily referral patients to 25. CONCLUSIONS: This research investigated the two-hospital patient referral problems. We conducted and analyzed a simulation model and improved the case hospital's conditions, enhancing the quality of its medical care. The findings of this study can extend to other departments or hospitals.

5.
Water Res ; 176: 115735, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32224330

RESUMO

Graphene oxide (GO) sheets are unstable in aqueous environments, and the effect of photo-transformation on GO toxicity to freshwater algae (Chlorella pyrenoidosa) was investigated. Our results demonstrated that GO underwent photo-reduction under 25-day sunlight irradiation, and the transformation was generally completed at Day 8. The toxicological investigation showed that 8-day sunlight irradiation significantly increased growth inhibition of GO (25 mg/L) to algal cells by 11.2%, due to enhanced oxidative stress and stronger membrane damage. Low molecular weight (LMW) species were produced during the 8-day GO transformation, and they were identified as two types of aromatic compounds, which played a crucial role in increasing toxicity. The combined toxicity of GO and Cu2+ ions before and after light irradiation was further investigated. Antagonistic effect was observed between the toxicity of pristine GO and co-existing Cu2+ ions. After co-irradiation of GO and Cu2+ ions for 8 days, their combined toxicity was unexpectedly lower or insignificant in comparison with the treatments of pristine GO, or pristine GO in the presence of Cu2+ ions. Two mechanisms were revealed for this finding: (1) Cu2+ ions suppressed the photo-transformation of GO; (2) the toxicity of free Cu2+ ions was decreased through the adsorption/retention of Cu2+ ions and formation of Cu-based nanoparticles (e.g., Cu2O and Cu2S) on the photo-transformed GO. The provided data are helpful for better understanding the environmental process and risk of GO under natural conditions.


Assuntos
Chlorella , Grafite , Poluentes Químicos da Água , Água Doce , Íons , Metais
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 622-628, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319406

RESUMO

OBJECTIVE: To investigate the factors affecting counting and collection efficiency of the final product- mononuclear cells (MNCs) in the collection of mononuclear cells for tumor cell biotherapy. METHODS: The collected data of 142 tumor patients and healthy donors were analyzed, including age, sex, height, weight, BMI, the total blood volume, diagnostic category, vascular access, operator, final product volume, ACD anticoagulant usage, flow rate and circulation times, pre-apheresis Hb, RBC, Plt, WBC, lymphocyte count, monocyte count, neutrophil count, circulating blood volume without anticoagulant, final product MNC and collection efficiency of MNC. CE(collection efficiency)%= final product MNC×100/(pre-apheresis MNC×circulating blood volume without anticoagulant). The factors affecting final products MNC and CE of MNC were detected by T test and multiple linear regression analysis. RESULTS: The CE of tumor patients was higher than that of healthy donors (24.41±1.91,vs 20.01±0.99),(P=0.043), and CE of MNC was different among different operators (P=0.01, H=18.59). There was a positive correlation of the final MNC with the volume of final product, ACD anticoagulant usage and pre-apheresis lymphocyte count (P= 0.00, P= 0.01, P= 0.00, r=0.811); CE of MNC negatively correlated with flow rate and pre-apheresis RBC, but positively correlated with operator's working age and ACD anticoagulant usage (P=0.01, P=0.04, P=0.03, P= 0.00, r=0.495). CONCLUSION: more higher pre-apheresis lymphocyte , more amount of the final product and ACD anticoagulant usage, and more high the final MNC. During the collecting process, more ACD anticoagulant usage and more high operator's seniority, lead to the higher MNC'S CE; while more high pre-apheresis RBC and more fast flow rate, cause the lower the CE of MNC.


Assuntos
Terapia Biológica , Remoção de Componentes Sanguíneos , Humanos , Leucaférese , Contagem de Leucócitos , Leucócitos Mononucleares , Linfócitos , Doadores de Tecidos
7.
Theriogenology ; 148: 103-111, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171969

RESUMO

Follicle-stimulating hormone (FSH) has been newly demonstrated to play a great role in promoting fat accumulation, providing a potential to target FSH for controlling fat accumulation and treating obesity. A short, 13-amino acid of FSHß (FSHß13AA) was indentified to be the FSH receptor-binding epitope in both humans and mice. By conservation analysis, we found such FSHß13AA is highly conserved across species. Accordingly, we designed a new FSH antigen by synthesizing a tandem of FSHß13AA (LVYKDPARPNIQK) and then conjugating it to ovalbumin (FSHß13AA-T-OVA). Then, we tested its efficacy in suppressing fat accumulation in both ovariectomized and intact mouse models. Vaccination with this novel antigen emulsified in mild adjuvant, Specol, was highly effective in preventing ovariectomy-induced body weight gain and fat accumulation in mice (P < 0.01). Mechanistically, FSH vaccination treatment inhibited lipid biosynthesis by inactivating PPARγ adipogenic signaling pathway and simultaneously enhanced adipocyte themogenesis via upregulating UCP1 expression in both visceral and subcutaneous adipose tissues. Moreover, injection of this novel FSH vaccine also substantially reduced (P < 0.05) fat accumulation in both intact male and female mice. These actions result from the specific binding of the generated antibody to the ß-subunit to block its action, rather than lowering the circulating levels of FSH, as evidenced by nearly no alterations in serum FSH levels in mice following FSH vaccination. Overall, we developed a novel FSH antigen and vaccine, and demonstrated it is highly efficacious in suppressing fat accumulation.

8.
Org Biomol Chem ; 18(10): 1900-1909, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32108203

RESUMO

Amide naphthotubes with four carboxylate sidechains have been reported by us for selectively recognizing hydrophilic molecules in water and they have found applications in sensing and self-assembly. Modification of these macrocycles on the sidechains would further expand their applicability. Herein, we report the synthesis of mono-functionalized amide naphthotubes with one alkyne and three carboxylate groups. These naphthotubes show rather different binding affinities from that of the amide naphthotubes with four carboxylate sidechains. The partial self-inclusion of the alkyne group in the cavity was invoked to explain these differences. In addition, the syn- and anti-configurational isomers of the naphthotubes with four carboxylate groups were found to be assigned incorrectly in our earlier publication. Further evidence is provided here for the new assignment. The implications of this new structural assignment for the conclusions drawn in the earlier works are discussed as well.

9.
Anal Chem ; 92(3): 2690-2696, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31913607

RESUMO

Discrimination of cancer cells at the single-cell metabolic level is crucial for early diagnosis. However, some cancer cells share similar metabolic information with normal cells, making them difficult to be distinguished using mass spectrometry. Herein, we propose a method by treating osteosarcoma cells and normal human osteoblasts with mannose as a stimulant, which greatly promotes the metabolic discrimination of osteosarcoma cells at the single-cell level. The low PMI (mannose 6-phosphate isomerase) level of both osteosarcoma cell lines compared to normal human osteoblasts is the reason for the abnormal metabolic pathway of two osteosarcoma cell lines with mannose treatment. We also found that the level of hexoses-6P in osteosarcoma cells significantly increased after mannose treatment, while no such increase was found in normal human osteoblasts. The proposed method is very meaningful for early diagnosis of cancer.

10.
Aging (Albany NY) ; 12(1): 672-689, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31927536

RESUMO

BACKGROUND: This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson's disease through down-regulating transcription factor specificity protein 1 (SP1). RESULTS: The successfully modeled rats with Parkinson's disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson's disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson's disease. CONCLUSION: Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson's disease by inhibiting SP1. METHODS: Parkinson's disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson's disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson's disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.

11.
Nanotoxicology ; 14(2): 162-180, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31703536

RESUMO

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

12.
Acc Chem Res ; 53(1): 198-208, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31858790

RESUMO

Macrocyclic hosts are the principal tools used in supramolecular chemistry because they can recognize other small molecules through non-covalent interactions. However, in terms of recognition ability, known macrocyclic hosts are often not comparable to bioreceptors. This may be due to the lack of functional groups inside the deep cavity, which is a common feature of bioreceptors. Most of the known macrocyclic hosts contain either a hydrophobic cavity or polar binding sites only. Macrocyclic hosts with functional groups inside a hydrophobic cavity are rare. In 2004, Glass and co-workers reported a pair of water-soluble naphthalene-based molecular tubes with amide protons in the well-defined deep cavity. The cavity feature is very similar to that of bioreceptors. However, the amide protons were not used in molecular recognition and were replaced in 2012 with allyl groups in order to improve the hydrophobic effect. We started our work on the basis of the Glass molecular tubes but paid close attention to the functional groups in the deep cavity. In this Account, we summarize our results on these biomimetic receptors, which we call naphthotubes. The inward-directed functional groups endow the corresponding naphthotubes with unique recognition abilities. Naphthotubes with hydrogen-bond acceptors (ether, ester, and imine) prefer to bind organic cations; naphthotubes with hydrogen-bond donors (urea, thiourea, and amide) can bind neutral molecules; amine naphthotubes are stimuli-responsive to acid/base. In particular, the water-soluble amide naphthotubes are able to selectively recognize highly hydrophilic molecules in water-a generally accepted challenge in supramolecular chemistry. The unique recognition ability of these naphthotubes provides the basis for their applications in sensing, self-assembly, and molecular machines. Fluorescent sensing of environmental contaminants in water, chiroptical sensing of small chiral molecules, allosteric cooperative self-assembly, dissipative self-assembly, and directional molecular shuttles have been demonstrated with these naphthotubes. Overall, we hope to convey the message that these naphthotubes have unique recognition properties and promising applications in diverse fields. We believe that further exploration of this class of macrocycles may lead to practical applications in, for example, biomedical science, environmental science, and other related fields.

13.
BMC Complement Altern Med ; 19(1): 360, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829159

RESUMO

BACKGROUND: Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). METHODS: A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. RESULTS: Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. CONCLUSIONS: LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.


Assuntos
Cardiotônicos/farmacologia , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Extratos Vegetais/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Animais , Coração/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , MicroRNAs , Proteínas Musculares/metabolismo , Miocárdio/química , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Retículo Sarcoplasmático/ultraestrutura
14.
Environ Monit Assess ; 191(10): 609, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486904

RESUMO

A study was performed to determine whether self-rooted grafting decreases cadmium (Cd) accumulation in post-grafting soybean (Glycine max (Linn.) Merrill) generations. Pot experiments were performed using ungrafted (UG) seedlings, self-rooted grafting from the same soybean seedling (SG), self-rooted grafting from two soybean seedlings at the same growth stage (TG), and self-rooted grafting from two soybean seedlings at different developmental stages (DG). Growth and Cd accumulation in three post-grafting soybean generations were assessed. In the SG treatment, only the second post-grafting generation had increased shoot biomass and only the first post-grafting generation shoots had decreased Cd contents. The seed Cd content, soluble protein content, and antioxidant enzyme activity were not significantly affected in three post-grafting generations. In the TG and DG treatments, shoot biomass, soluble protein content, and antioxidant enzyme activities were increased, and the shoot and seed Cd contents were decreased in three post-grafting generations. The seed Cd contents in the first, second, and third post-grafting generations were 15.00%, 9.46%, and 12.44%, respectively, lower in the TG than UG treatments. The seed Cd contents in the first, second, and third post-grafting generations were 32.73%, 27.03%, and 32.22%, respectively, lower in the DG than UG treatments. Different grafting methods promoted growth and decreased Cd accumulation to different degrees in three post-grafting generations. Grafting seedlings at different developmental stages had the strongest effects.


Assuntos
Agricultura/métodos , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Soja/crescimento & desenvolvimento , Soja/metabolismo , Biomassa , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Sementes/metabolismo
15.
Cell Mol Neurobiol ; 39(7): 1069, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414301

RESUMO

The original version of this article unfortunately contained an error in author group. The authors Yi-Xiang See, Xin Chen, Zi-Kai Chen and Ze-Bin Huang were inadvertently included in the article.

16.
Chem Commun (Camb) ; 55(73): 10924-10927, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441488

RESUMO

Two positively-charged naphthotubes with imidazolium as the bridges were synthesized and their structures have been characterized by 1H NMR, MS, and X-ray crystallography. These naphthotubes are capable of binding aromatic hydrocarbons. Surprisingly, the binding affinities are much higher in CD3CN than in CD2Cl2. The solvent effect on the ion pairing interactions and competitive binding of CD2Cl2 was invoked to explain this unusual phenomenon.

17.
Mol Cell ; 75(6): 1188-1202.e11, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31399345

RESUMO

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.


Assuntos
5-Metilcitosina/metabolismo , Embrião não Mamífero/embriologia , Desenvolvimento Embrionário/fisiologia , Estabilidade de RNA/fisiologia , RNA Mensageiro Estocado/metabolismo , Peixe-Zebra/embriologia , Animais , Células HeLa , Humanos , Camundongos , RNA Mensageiro Estocado/genética , Peixe-Zebra/genética
18.
Beilstein J Org Chem ; 15: 1460-1467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354862

RESUMO

Two new tetralactam macrocycles with 2,3-dibutoxynaphthalene groups as sidewalls have been synthesized and characterized. The macrocycle containing isophthalamide bridges can bind square-planar chloride coordination complexes of gold(III), platinum(II), and palladium(II) in CDCl3, while the macrocycle with 2,6-pyridine dicarboxamide bridging units cannot. This may be due to the shrunken cavity caused by intramolecular hydrogen bonds in the latter tetralactam macrocycle. The binding of the isophthalamide-based macrocycle is mainly driven by hydrogen bonds and electrostatic interactions. This naphthalene-based macrocycle has similar binding affinities to all the three abovementioned precious metal chloride complexes. This is in contrast to the fact that the tetralactam macrocycle with anthracene as the sidewalls only show good binding affinities to AuCl4 -. The superior binding to all three complexes may be due to the conformational diversity of the naphthalene-based macrocycle, which make it conformationally adaptive to maximize the binding affinities. In addition, the macrocycle shows fluorescent quenching when adding the chloride metal complexes in its solution and may be used as a fluorescent sensor for the detection of these coordination complexes.

19.
Int Immunopharmacol ; 75: 105734, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301558

RESUMO

This study is conducted to investigate the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in the protection of dopaminergic neurons in Parkinson's disease (PD) through regulating the PI3K/Akt signaling pathway. PD rat model was induced by injection of 6-hydroxydopamine (6-OHDA) to damage the substantia nigra striatum. The successfully modeled PD rats were introduced with siRNA-negative control (NC) or UCA1-siRNA. The expression of UCA1 in neurobehavioral change, neuroinflammatory response and oxidative stress of PD rats were explored. The effect of UCA1 on the PI3K/Akt signaling pathway and downstream proteins IκBα and ERK was also investigated. The rats with PD exhibited aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress. Down-regulation of UCA1 up-regulated the expression of TH positive cells and DA content, reduced the apoptosis of substantia nigra neurons, the apoptosis of substantia nigra neurons and oxidative stress and improved the neuroinflammatory response in PD rats. Down-regulation of UCA1 inhibited the activation of the PI3K/AKT signaling pathway in substantia nigra of PD rats. Our study suggests that the downregulated lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in PD rats through the inhibition of the PI3K/Akt signaling pathway.


Assuntos
Transtornos Parkinsonianos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Animais , Neurônios Dopaminérgicos/patologia , Regulação para Baixo , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Estresse Oxidativo , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/patologia , RNA Interferente Pequeno/genética , Ratos Wistar , Transdução de Sinais , Substância Negra/metabolismo
20.
Anal Chem ; 91(15): 9777-9783, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31242386

RESUMO

Comprehensive analysis of single-cell metabolites is critical since differences in cellular chemical compositions give rise to specialized biological functions. Herein, we propose a label-free mass cytometry by coupling flow cytometry to ESI-MS (named CyESI-MS) for high-coverage and high-throughput detection of cellular metabolites. Cells in suspension were isolated, online extracted by sheath fluid, and lysed during gas-assisted electrospray, followed by real-time MS analysis. Hundreds of metabolites, including nucleotides, amino acids, peptides, carbohydrates, fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids, were detected and identified from one single cell. Discrimination of four types of cancer cell lines and even three subtypes of breast cancer cells was readily achieved using their distinct metabolic profiles. Furthermore, we screened out 102 characteristic ions from 615 detected peak signals for distinguishing breast cancer cell subtypes and identified 40 characteristic molecules which exhibited significant differences among these subtypes and would be potential metabolic markers for clinical diagnosis. CyESI-MS is expected to be a new-generation mass cytometry for studying cell heterogeneity on the metabolic level.

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