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Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.
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BACKGROUND: The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. METHODS: In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. RESULTS: We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). CONCLUSION: Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Feminino , Humanos , Masculino , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Linfócitos B , RecidivaRESUMO
Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU_trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.
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Anemarrhena , Anemarrhena/química , Código de Barras de DNA Taxonômico , Variação Genética , China , FilogeniaRESUMO
BACKGROUND: The purpose of this study was to explore the role of FOXO3 in gastric cancer (GC). METHODS: Data on gastric cancer and normal tissues were collected from the TCGA and GTEx databases. Survival analysis was performed with the Kaplan-Meier method, and the ENCORI online analysis tool was used to predict potential interaction miRNA. The MCPCOUNTER and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to predict the relationship between immune infiltration and FOXO3. Finally, gene set enrichment analysis (GSEA) was used to explore the potential pathways of FOXO3 during the development of GC. RESULTS: We found that mRNA expression level of FOXO3 was remarkably higher in tumor tissue than in normal tissue, and poor prognoses of GC patients were correlated with higher expression of FOXO3. We also found that hsa-miR-18a-5p and hsa-miR-18b-5p can interact with FOXO3 and that high expression of hsa-miR-18a-5p and hsa-miR-18b-5p predicted better prognoses in GC patients. TP53 mutation was significantly associated with high FOXO3 expression, while ARID1A mutation was associated with low FOXO3 expression. Multiple immune cells were found to be related to the expression of FOXO3, and lower expression of FOXO3 may be better suited to immune checkpoint blockade treatment. CONCLUSIONS: We find that FOXO3 is a potential oncogene and that the transcript level of FOXO3 is related to the mutation of TP53 and ARID1A. In addition, FOXO3 may influence immune infiltration and different signal pathways through sponge adsorption of miRNA to impact the prognoses of stomach adenocarcinoma patients.
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Adenocarcinoma , MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , MicroRNAs/genética , Algoritmos , Proteína Forkhead Box O3/genéticaRESUMO
MgH2 is well known as a potential hydrogen storage material. However, its high thermodynamic stability, high dissociation temperature, slow absorption, and desorption kinetics severely limit its application. Aiming at these shortcomings, we try to improve the hydrogen storage property of MgH2 by doping with transition metal Sc atoms. The structures and electronic and hydrogen storage properties of Mg-Sc-H systems have been systematically studied by combining the crystal structure analysis by particle swarm optimization and density functional theory method. The results show that the structure of MgScH8 with the R3 space group is the most stable one, which is proved to be a wide-band gap (2.96 eV) semiconductor. The possible decomposition pathways, which are crucial for the applicability of R3-MgScH8 as a hydrogen storage material, are studied, and the pathway of MgScH8 â ScH6 + Mg + H2 is found to be the most favorable one under 107.8 GPa pressure, while above 107.8 GPa, MgScH8 â Mg + Sc + 4H2 becomes the most thermodynamically stable pathway and releases the maximum amount of hydrogen. Based on the root mean square deviation calculation, it is found that R3-MgScH8 begins to melt at 400 K. The result of ab initio molecular dynamics simulations shows that the hydrogen release capacity (4.04 wt %) can be easily achieved at 500 K, thus making MgScH8 a potential hydrogen storage material.
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The potential applications of Ir2P are promising due to its desirable hardness, but its fundamental properties are still not fully understood. In this study, we present a systematic investigation of Ir2P's structural, electronic, superconducting, optical, and thermodynamic properties of Ir2P under pressure. Our calculations show that Ir2P has a Fm3Ìm structure at ambient pressure, which matches well with experimental data obtained from high-pressure synchrotron X-ray diffraction. As pressure increases, a transition from the Fm3Ìm to the I4/mmm phase occurs at 103.4 GPa. The electronic structure and electron-phonon coupling reveal that the Fm3Ìm and I4/mmm phases of Ir2P are superconducting materials with superconducting transition temperatures of 2.51 and 0.89 K at 0 and 200 GPa, respectively. The optical properties of Ir2P indicate that it has optical conductivity in the infrared, visible, and ultraviolet regions. Additionally, we observed that the reflectivity R(ω) of Ir2P is higher than 76% in the 25-35 eV energy range at different pressures, which suggests that it could be used as a reflective coating. We also explored the finite-temperature thermodynamic properties of Ir2P, including the Debye temperature, the first and second pressure derivatives of the isothermal bulk modulus, and the thermal expansion coefficient up to 2000 K using the quasi-harmonic Debye model. Our findings offer valuable insights for engineers to design better devices.
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The Ca9.95-x Na0.75 K0.25 (PO4)7: Eu.0.05(2+), Mn(x)2+ (x = 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6 and 0.7) phosphors were synthesized by high temperature solid-state reaction, and their phase composition and fluorescence emission properties were studied. Due to the existence of double phases with similar crystal structure, the 5d-4f transition of Eu2+ ions in the phosphors emits a fluorescence of wide wavelength with peaks located at 491 nm and 540 nm respectively. The energy transfer between Eu2+ and Mn2+, together with the occupation of Mn2+ ions at the eight coordination sites in the phosphors, makes the 4T1 (4G)-6A1 (6S) transition of Mn2+ ions eimit red emission peaked at 635 nm. The combination of fluorescence emtted by Mn2+ and Eu2+ ions results in the emission of white light with color coordinates (0.3335, 0.2924), (0.3999, 0.3179) and (0.3307, 0.2564). The nearly pure white light emitting makes the phosphors show great application potential in the white light-emitting LEDs.
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The Ba1.97 Ca1-x (B3O6)2 : Eu2+, Mn(x)2+ (x = 0, 0.03, 0.06, 0.15) phosphors were synthesized by high temperature solid-state reaction, and their phase composition and luminescence properties were studied. In these phosphors, Eu2+ locates at the crystal sites of Ba2+ and Ca2+ ions. Under 317 nm UV light excitation, the 5d --> 4f transition of Eu2+ forms a broad blue emission band with a peak at 450 nm. With the energy transfer from Eu2+ ions, Mn2+ ions emit a broad red band with the peak at 600 nm. The mixture of the broad blue emission and a broad red emission forms an approximate white light with the CIE chromaticity (x = 0.371, y = 0.282). The phosphors can be excited effectively by UV light in the range of 250-400 nm, so they are the potential candidates for single white light-emitting phosphor excited by UV-LED.
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The structural phase transition, ferroelectric polarization, and electric properties have been investigated for photovoltaic films CsMI3 (M = Pb, Sn) epitaxially grown along (001) direction based on the density functional theory. The calculated results indicate that the phase diagrams of two epitaxial CsPbI3 and CsSnI3 films are almost identical, except critical transition strains varying slightly. The epitaxial tensile strains induce two ferroelectric phases Pmc21, and Pmn21, while the compressive strains drive two paraelectric phases P212121, P21212. The larger compressive strain enhances the ferroelectric instability in these two films, eventually rendering them another ferroelectric state Pc. Whether CsPbI3 or CsSnI3, the total polarization of Pmn21 phase comes from the main contribution of B-position cations (Pb or Sn), whereas, for Pmc21 phase, the main contributor is the I ion. Moreover, the epitaxial strain effects on antiferrodistortive vector, polarization and band gap of CsMI3 (M = Pb, Sn) are further discussed. Unusual electronic properties under epitaxial strains are also revealed and interpreted.
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Long, highly stable, and densely packed edge-on nanocolumns of hexa-peri-hexabenzocoronenes spontaneously grow from solution as self-assembled monolayers chemisorbed on gold.
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The kinetics of phase transformation from the liquid crystalline mesophase to the crystalline phase has been studied in a model dipole-functionalized hexabenzocoronene derivative by x-ray diffraction, solid state NMR recoupling techniques, and dielectric spectroscopy. These probes revealed long-lived metastability and an intermediate state involving a change in the unit cell prior to crystallization. The barrier properties were dominant and amount to 1 and 2.5 eV, respectively, for the unit cell transformation and crystallization processes. These effects should be considered in the design of discotic liquid crystals for electronic applications.
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We perform the first-principles calculations combined with the particle swarm optimization algorithm to investigate the high-pressure phase diagrams of Na[Formula: see text]F3 ([Formula: see text] = Mn, Ni, Zn). Two reconstructive phase transitions are predicted from Pv-[Formula: see text] to pPv-[Formula: see text] at about 9 GPa and pPv-[Formula: see text] to ppPv-[Formula: see text] at around 26 GPa for NaZnF3. That is not the case for NaMnF3-a direct transition (reconstructive transition in nature but with the same Pnma space group) from Pv-[Formula: see text] to ppPv-[Formula: see text] phase around 12 GPa. Strikingly, our simulated results manifest that a disproportionation phase of NaZnF3 post-perovskite is uncovered along the way, which provides a successful explanation for the observed results in experiment. Additionally, the mechanical and thermal properties, especially the dynamical property, of the four NaZnF3 phases have also been studied. Here, we reveal the obvious softening of [Formula: see text]-wave velocity and bulk sound speed in pPv-[Formula: see text]-to-ppPv-[Formula: see text] transition, which may result in the discontinuity of seismic waves propagation through the Earth's interior.
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A new synthetic strategy toward novel linear two-dimensional graphene nanoribbons up to 12 nm has been established. The nanoribbons are characterized by MS, UV/vis, and scanning tunneling microscopy (STM). Various microscopic studies of these novel structures showed a high tendency to self-assemble.
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The self-assembly, the molecular dynamics, and the kinetics of structure formation are studied in dipole-functionalized hexabenzocoronene (HBC) derivatives. Dipole substitution destabilizes the columnar crystalline phase except for the dimethoxy- and monoethynyl-substituted HBCs that undergo a reversible transformation to the crystalline phase. The disk dynamics are studied by dielectric spectroscopy and site-specific NMR techniques that provide both the time-scale and geometry of motion. Application of pressure results in the thermodynamic phase diagram that shows increasing stability of the crystalline phase at elevated pressures. Long-lived metastability was found during the transformation between the two phases. These results suggest new thermodynamic and kinetic pathways that favor the phase with the highest charge carrier mobility.
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An anaerobic-aerobic process including a fresh refuse landfill reactor as denitrifying reactor, a well-decomposed refuse reactor as methanogenesis reactor and an aerobic activated sludge reactor as nitrifying reactor was operated by leachate recirculation to remove organic and nitrogen simultaneously. The results indicated that denitrification and methanogenesis were carried out successfully in the fresh refuse and well-decomposed landfill reactors, respectively, while the nitrification of NH(4)(+)-N was performed in the aerobic reactor. The maximum organic removal rate was 1.78 kg COD/m(3)d in the well-decomposed refuse landfill reactor while the NH(4)(+)-N removal rate was 0.18 kg NH(4)(+)-N/m(3)d in the aerobic reactor. The biogas from fresh refuse reactors and well-decomposed refuse landfill reactors were consisted of mainly carbon dioxide and methane, respectively. The volume fraction of N(2) increased with the increase of NO(3)(-)-N concentration and decreased with the drop of NO(3)(-)-N concentration. The denitrifying bacteria mustered mainly in middle layer and the denitrifying bacteria population had a good correlation with NO(3)(-)-N concentration.
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Aerobiose , Anaerobiose , Nitrogênio/isolamento & purificação , Compostos Orgânicos/isolamento & purificação , Eliminação de Resíduos , Conservação dos Recursos NaturaisRESUMO
A simple dimethoxy-substituted hexa-peri-hexabenzocoronene (m-dimethoxy HBC) was unexpectedly obtained along with a bis-spirocyclic dienone during an intramolecular Scholl reaction of its para isomer.
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Enhancing the treatment efficiency of livestock wastewater by effluent recirculation is investigated in a pilot-scale vertical-flow constructed wetland. The wetland system is composed of downflow and upflow stages, on which narrow-leaf Phragmites communis and common reed Phragmites typhia are planted, respectively; each stage has a dimension of 4 m(2) (2 m x 2 m). Wastewater from the facultative pond is fed into the system intermittently at a flow rate of 0.4 m(3)/d. Recirculation rates of 0, 25%, 50%0, 100% and 150% are adopted to evaluate the effect of the recirculation rate on pollutants removal. This shows that with effluent recirculation the average removal efficiencies of NH4-N, BOD5 and SS obviously increase to 61.7%, 81.3%, and 77.1%, respectively, in comparison with the values of 35.6%o, 50.2%, and 49.3% without effluent recirculation. But the improvement of TP removal is slight, only from 42.3% to 48.9%. The variations of NH4-N, DO and oxidation-reduction potential (ORP) of inflow and outflow reveal that the adoption of effluent recirculation is beneficial to the formation of oxide environment in wetland. The exponential relationships with excellent correlation coefficients (R(2) > 0.93) are found between the removal rates of NH4-N and BOD5 and the recirculation rates. With recirculation the pH value of the outflow decreases as the alkalinity is consumed by the gradually enhanced nitrification process. When recirculation rate is kept constant at 100%, the ambient temperature appears to affect NH4-N removal, but does not have significant influence on BOD5 removal.
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Animais Domésticos , Eliminação de Resíduos Líquidos/normas , Água/análise , Agricultura/normas , Animais , China , Monitoramento Ambiental/métodos , Poluentes Ambientais/análiseRESUMO
OBJECTIVE: To observe the effect of Zhuang-medical thread moxibustion combined with needle-pricking on vascular oxidative stress injury in oxidative stress injury rats. METHODS: Eighty Wistar rats were randomly allocated to normal control, sham operation (sham), model, and combined treatment groups (n=20 in each group). The oxidative stress injury model was established by ligation of the left sciatic nerve to induce chronic constriction injury (CCI) pain stress stimulation. Zhuang-medical thread moxibustion was applied to bilateral "Zusanli" (ST 36), once a day for 3 weeks. Needle-pricking was applied to left "Yanglingquan" (GB 34) and left "Huantiao" (GB 30), once a day for 3 weeks except Sundays. Plasma 6-keto-PGF 1α, thromboxane B 2 (TXB 2), NO and ET contents were assayed by radioimmunoassay. COX-2 immunoactivity of the femoral artery was determined by immunohistochemistry, and pathological changes of the femoral artery were detected by H. E. staining. RESULTS: Compared with the control group, the levels of plasma 6-keto-PGF 1α and NO in the model group were significantly reduced (P<0.05), while those of plasma TXB 2 and ET and COX-2 expression in the femoral artery were obviously increased in the model group (P<0.01). After moxibustion plus needle-pricking treatment, CCI-induced decrease of plasma 6-keto-PGF 1α and NO contents, and increase of plasma TXB 2 and ET and COX-2 expression levels were obviously reversed (P<0.05, P<0.01). The tubal wall of the femoral artery in rats of the model group got thicker, while that of the combined treatment group was relatively thinner, suggesting an inhibition of vascular intimal hyperplasia after the treatment. CONCLUSION: Zhuang-medical thread moxibustion combined with needle-pricking of ST 36, GB 34 and GB 30 can reduce the expression of femoral artery COX-2 and regulate the balance of both plasma PGI 2/TXA 2 and plasma NO/ET in CCI-induced oxidative stress rats, which may contribute to its effect in suppressing oxidative stress-induced vascular intimal hyperplasia.
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Terapia por Acupuntura , Vasos Sanguíneos/lesões , Moxibustão , Estresse Oxidativo , Doenças Vasculares/terapia , Pontos de Acupuntura , Animais , Vasos Sanguíneos/enzimologia , Vasos Sanguíneos/metabolismo , Terapia Combinada , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Masculino , Ratos , Ratos Wistar , Tromboxano B2/sangue , Doenças Vasculares/enzimologia , Doenças Vasculares/metabolismoRESUMO
OBJECTIVE: To observe the effect of needle pricking therapy on the expression of thymic stromal lymphopoietin (TSLP) protein, T-box expressed in T cells(T-bet)mRNA and GATA-binding protein-3 (GATA 3) mRNA in the lung tissue of mice with asthma, so as to explore its mechanism underlying improvement of asthma. METHODS: Thirty female BALB/c mice were randomly divided into control, model and needle pricking groups (10 mice/group). The asthma model was established by i. p. of Ovalbumin (OVA) suspension fluid (containing Aluminium Hydroxide 400 microg and OVA 100 microg, 50 microg/L) and forced inhalation of atomized OVA. A sharp needle was held to prick "Dazhui" (GV 14),"Feishu" (BL 13), "Dingchuan" (EX-B 1),"Fengmen" (BL 12),"Shenshu" (BL 23) and "Pishu" (BL 20) acupoint regions to let a little bit of white fibrous tissue out, then to insert into the acupoints to about 1 mm in depth, once a day for seven times. The lung tissue was taken for detecting the expression of T-bet mRNA and GATA-3 mRNA by RT-PCR and for determining the immunoactivity of TSLP by immunofluorescence method. In addition, HE staining was used to examine the pathologic changes of the lung tissue. RESULTS: Compared with the control group, the expression levels of GATA-3 mRNA and TSLP protein of the lung tissue in the model group were significantly increased (P < 0.01), whereas that of T-bet mRNA was remarkably decreased (P < 0.05). Following needle prick stimulation treatment, the expression levels of GATA-3 mRNA and TSLP protein were markedly down-regulated (P < 0.01) and that of T-bet mRNA was obviously upregulated (P < 0.05). After the treatment, pathological changes including hyperemia of the pulmonary alveoli, epithelial thickening, narrowing of the lumina, and infiltration of many inflammatory cells around the tracheal blood vessels were improved. CONCLUSION: Needle pricking therapy can regulate the expression of pulmonary TSLP protein and GATA 3 and T-bet genes in mice with asthma, which may contribute to its effect in improving pulmonary pathological changes of asthma mice.
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Terapia por Acupuntura , Asma/terapia , Citocinas/metabolismo , Fator de Transcrição GATA3/metabolismo , Pulmão/metabolismo , Proteínas com Domínio T/metabolismo , Pontos de Acupuntura , Animais , Asma/genética , Asma/metabolismo , Citocinas/genética , Feminino , Fator de Transcrição GATA3/genética , Regulação da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas com Domínio T/genética , Células Th2/metabolismo , Linfopoietina do Estroma do TimoRESUMO
Strong dipole moments have been built into two hexa-peri-hexabenzocoronene (HBC) derivatives (1 and 2) originating from the push-pull structure of the molecules with one electron-donating and one electron-withdrawing substituent. The influence of dipole moment on the self-assembly of HBCs in solution and in bulk has been investigated.