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1.
Opt Express ; 32(3): 3989-3996, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297608

RESUMEN

With the rapid development of superconducting quantum computing and the implementation of surface code, large-scale quantum computing is emerging as an urgent demand. In a superconducting computing system, the qubit is maintained in a cryogenic environment to avoid thermal excitation. Thus, the transmission of control signals, which are generated at room temperature, is needed. Typically, the transmission of these signals to the qubit relies on a coaxial cable wiring approach. However, in a large-scale computing system with hundreds or even thousands of qubits, the coaxial cables will pose great space and heat load to the dilution refrigerator. Here, to tackle this problem, we propose and demonstrate a direct-modulation-based optical transmission line. In our experiment, the average single-qubit XEB error and control error are measured as 0.139% and 0.014% separately, demonstrating the feasibility of the optical wiring approach and paving the way for large-scale superconducting quantum computing.

2.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2522-2531, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812148

RESUMEN

Based on the R language data mining technology, the medication rules of traditional Chinese medicine(TCM) in the treatment of H-type hypertension were discussed, and the basis and new ideas for the treatment of H-type hypertension with TCM were provided. CNKI, Wanfang, VIP, and SinoMed were searched to collect clinical studies on the treatment of H-type hypertension with TCM. The data were screened, and Excel was used to build a database. Rstudio was used to carry out drug efficacy classification, four Qi and five flavors, meridian homing, frequency of use, correlation, association rules, and clustering analyses of drugs and explore the medication rules of TCM. 191 TCM prescriptions were obtained, and the main syndromes were phlegm-dampness accumulation syndrome, phlegm and blood stasis syndrome, and Yin deficiency and Yang hyperactivity syndrome. A total of 169 kinds of TCM were used, and the frequency was 1 875 times. Among them, the drugs whose single use frequency was more than 20 times were high-frequency medicines, 26 kinds in total. They were Gestrodiae Rhizoma, Poria, Pinelliae Rhizoma, Achyranthis Bidenthis Radix, Glycyrrhizae Radix et Rhizoma, etc. The efficacy of high-frequency medicines was mainly classified as tonic medicines, blood-activating and stasis-removing medicines, liver-relieving wind medicines, and damp-clearing medicines. The four Qi of the drug were mainly warm and flat, and the five flavors were mainly sweet and bitter. The liver meridian and spleen meridian were the main meridians. The association rule analysis obtained a total of 14 groups of commonly used drug combinations, and the correlation analysis obtained 20 drug combinations with a high correlation coefficient. A total of six drug combinations were obtained by cluster analysis. Eight groups of drug pairs were obtained by association rule analysis on H-type hypertension with phlegm-dampness accumulation syndrome. Seven drug combinations with high correlation coefficients were obtained by correlation analysis, and three drug prescriptions were obtained by cluster analysis. The pathological factors of H-type hypertension are mainly phlegm, stasis, and deficiency. The disease site is in the liver, involving the spleen, lungs, and other viscera. The commonly used drugs are Gestrodiae Rhizoma, Poria, Pinelliae Rhizoma, Achyranthis Bidenthis Radix, etc. Banxia Baizhu Tianma Decoction, Tianma Gouteng Decoction, and Buyang Huanwu Decoction are commonly used prescriptions. The medication rules shown in this study can provide certain ideas for the clinical treatment of H-type hypertension with TCM.


Asunto(s)
Minería de Datos , Medicamentos Herbarios Chinos , Hipertensión , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Hipertensión/tratamiento farmacológico , Medicina Tradicional China
3.
Opt Express ; 31(16): 26301-26313, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710493

RESUMEN

We have developed a simple time-bin phase encoding quantum key distribution system, using the optical injection locking technique. This setup incorporates both the merits of simplicity and stability in encoding, and immunity to channel disturbance. We have demonstrated the field implementation of quantum key distribution over long-distance deployed aerial fiber automatically. During the 70-day field test, we achieved approximately a 1.0 kbps secure key rate with stable performance. Our work takes an important step toward widespread implementation of QKD systems in diverse and complex real-life scenarios.

4.
Opt Express ; 31(16): 26335-26343, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710496

RESUMEN

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

5.
Biochem Genet ; 61(6): 2382-2400, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37060482

RESUMEN

Oil palm (Elaeis guineensis) is the most important tropical oil-bearing crop species worldwide. MADS-box proteins, which play crucial roles in plant growth and development and are involved in various physiological and biochemical processes, compose one of the largest families of plant transcription factors. In this study, 42 MADS-box genes were screened from the mesocarp transcriptome database of oil palm fruit, and their phylogenetic relationships with Arabidopsis thaliana MADS-box genes were analyzed. Based on the results, MADS-box genes from oil palm mesocarp were classified into four groups: MIKCc-type, MIKC*-type, Mα-type, and Mγ-type MADS-box genes. Members of the subfamilies were classified according to the presence of three specific protein motifs. To explore the differential expression of the MADS-box genes, the dynamic expression of all selected MADS-box genes in oil palm was measured by RNA-seq. The high expression of specific MADS-box genes in the mesocarp of oil palm during different developmental stages indicates that those genes may play important roles in the cell division of and metabolite accumulation in the fruit and could become important targets for fruit development and oil accumulation research in oil palm.


Asunto(s)
Arecaceae , Frutas , Frutas/metabolismo , Filogenia , Factores de Transcripción/genética , Secuencias de Aminoácidos , Arecaceae/genética , Arecaceae/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
6.
Drug Dev Res ; 84(1): 110-120, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36433708

RESUMEN

In this work, a series of indole-containing pyrazole-carbohydrazide derivatives A1-A25 were synthesized, and their biological activity on tubulin polymerization inhibition and mitotic catastrophe was evaluated. For introducing indole group to CA-4 pattern, the carbohydrazide linker was used for the first time. As the top hit, A18 suggested notable antiproliferation efficacy and tubulin polymerization inhibitory activity. Inferring comparable antitubulin effect with the positive control Colchicine, A18 indicated obviously lower cyto-toxicity. The cell scratch test showed that A18 could block the cell migration, while the confocal imaging depicted that A18 could induce the mitotic catastrophe via a Colchicine-like approach. The docking simulation visualized the probable binding pattern of A18. With the information in this work, some new hints on modification might be involved in further tubulin-related investigations.


Asunto(s)
Antineoplásicos , Moduladores de Tubulina , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/metabolismo , Tubulina (Proteína)/metabolismo , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Colchicina/farmacología , Indoles/farmacología , Pirazoles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Relación Estructura-Actividad
7.
J Stroke Cerebrovasc Dis ; 32(1): 106892, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36402093

RESUMEN

OBJECTIVES: Ischemia/reperfusion can induce neuronal apoptosis in the brain and lead to function deficits. The activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is neuroprotective against transient cerebral ischemia. The neuroprotective mechanisms of PKA mainly involve the regulation of gene transcription via the PKA/CREB pathway. The present study aims to investigate the neuroprotective effect of meglumine cyclic adenylate, an activator of PKA, under a rat model of global cerebral ischemia/reperfusion and to reveal the underlying mechanism involving signal transducer and activator of transcription 3 (STAT3)-Ser727 phosphorylation and mitochondrion modulation. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 15 min global cerebral ischemia, and meglumine cyclic adenylate was treated through tail intravenous injection 30 min before ischemia. Cresyl violet staining was used to evaluate neuron injury at 5 d of reperfusion. Western blotting was used to detect p-Ser727-STAT3, total STAT3, cytochrome c (Cyt c) and active caspase-3 in the tissues of hippocampal CA1 region at 6 h of reperfusion. STAT3-S727A was overexpressed in HT22 cells to reveal the significance of STAT3-Ser727 phosphorylation in the neuroprotective effect of meglumine cyclic adenylate. RESULTS: Pretreatment with meglumine cyclic adenylate not only significantly ameliorated neuron loss in CA1 region after global cerebral ischemia but also enhanced STAT3-Ser727 phosphorylation, increased mitochondrial STAT3, and decreased cytosolic Cyt c and active caspase-3. Overexpression of STAT3-S727A in HT22 cells eliminated meglumine cyclic adenylate-induced increase of p-Ser727-STAT3, mitochondrial STAT3, cytosolic Cyt c and active caspase-3. CONCLUSION: Meglumine cyclic adenylate protects neurons against ischemia/reperfusion injury via promoting p-Ser727-STAT3-associated mitochondrion modulation and inhibiting apoptosis pathway.


Asunto(s)
Isquemia Encefálica , Fármacos Neuroprotectores , Daño por Reperfusión , Ratas , Masculino , Animales , Fármacos Neuroprotectores/farmacología , Ratas Sprague-Dawley , Fosforilación , Caspasa 3/metabolismo , Factor de Transcripción STAT3/metabolismo , Apoptosis , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo
8.
Soft Matter ; 18(28): 5185-5193, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35726541

RESUMEN

Liquid metals have unique qualities for developing new generation soft functional devices. Here, we propose that the oscillation of liquid metals induced by a DC voltage could be employed to make a frequency response electronic system, which differs in principle from conventional rigid devices. A novel resonance phenomenon in which stimulating an LM droplet with a DC voltage in a particular structure would exhibit a similar electrically ignited beating heart effect is discovered. Moreover, a tunable liquid metal electronic oscillator is demonstrated based on the resonance of the liquid metal droplet, which can directly transform the DC voltage into an AC signal without complex auxiliary components. The fabricated liquid metal electronic oscillator is constructed to produce a square wave with an oscillation frequency range spanning from 20 to 80 Hz under different droplet masses. Besides, the duty ratio of the signal generated by the liquid metal electronic oscillator can be conveniently regulated in the range of 25-70% while the frequency remains relatively stable. This work suggests a new type of field-controlled liquid metal droplet resonance in the field of signal generators that can be applied to future soft robotics, smart digital microfluidics, and more intelligent systems.

9.
Bioorg Chem ; 121: 105665, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35152138

RESUMEN

Berberine is a quaternary isoquinoline alkaloid that exhibits potent hypoglycemic and hypolipidemic activity. Many medicinal chemists are currently working on structural modifications around the parent scaffold of berberine, expecting to further enhance its hypolipidemic activity and reducing its cytotoxicity. In this study, a focused berberine-like compound library containing 12,600 molecules was built via the introduction of various "drug-like" fragments at the C8 and C9 positions of berberine. Sixteen comopounds were hit by using the in-house QSAR models previously reported by our group. Considering synthesis feasibility and the cost of building-blocks, only four berberine analogs (library ID: 2028, 3847, 6033, and 12456) were selected and synthesized for investigating their lipid-lowering activities. Preliminary lipid-lowering study showed that compound 12456 with the phenylsulfonyl group at the C9 position had potent cholesterol inhibitory activity in HepG2 cells, superior to that of the parent compound berberine. Subsequently, a total of twenty-five 9-O-phenylsulfonyl-berberines (1a-1y) and twenty-four 9-O-phenylsulfonyl-tetrahydroberberine (2a-2x) were designed, synthesized, and evaluated by lipid-lowering experiments. The results displayed that most compounds exhibited more lipid-lowering activities than berberine. Among them, compound 1m inhibited cholesterol production close to 50% in both cell models when compared with the blank control; the inhibition of triglycerides exceeded 70%. Moreover, 1m also had significant pharmacological effects on the inhibition of LDLC and promotion of HDLC production, especially in the HepG2 cell model, in which the inhibitory rate against LDLC was close to 70% and the increase rate of HDLC was more than 75%. The hypolipidemic experiment of SD rats demonstrated that after 40 days of administration (1m, 15 mg/kg/d), blood cholesterol was reduced by 19.6%, triglycerides reduced by 34.52%, and LDLC reduced by 41.49%, when compared with the high-fat diet model (HFD). In addition, after 80 days of administration, the three indexes of 1m were still better than that of berberine. Oil Red O staining and H&E staining results showed that 1m exhibited potent lipid scavenging activity. All in all, 1m was discovered and identified as a potent lipid-lowering agent and a new berberine-like candidate, being evaluated by subsequent studies.


Asunto(s)
Berberina , Animales , Berberina/química , Berberina/farmacología , Colesterol , Hipolipemiantes/química , Hipolipemiantes/farmacología , Ratas , Ratas Sprague-Dawley , Triglicéridos
10.
Plant Cell Rep ; 41(6): 1449-1460, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35362736

RESUMEN

KEY MESSAGE: EgMYB108 regulates VLCFA anabolism in oil palm. Very long-chain fatty acids (VLCFAs), which are fatty acids with more than 18 C, can not only be used as a form of triglyceride (TAG) but also provide precursors for the biosynthesis of cuticle wax, and they exist in plant epidermal cells in the form of wax in higher plants. However, which and how transcriptional factors (TFs) regulate this process is largely unknown in oil palm. In this study, a MYB transcription factor (EgMYB108) with high expression in the mesocarp of oil palm fruit was characterized. Overexpression of EgMYB108 promoted not only total lipid content but also VLCFA accumulation in oil palm embryoids. Subsequently, transient transformation in protoplasts and qRT-PCR analysis indicated that the EgKCS5 and EgLACS4 genes were significantly increased with the overexpression of EgMYB108. Furthermore, yeast one­hybrid assays, dual-luciferase assays and EMSAs demonstrated that EgMYB108 binds to the promoters of EgKCS5 and EgLACS4 and regulates their transcription. Finally, EgMYB108 interacts with the promoters of EgLACS and EgKCS simultaneously and finally improves the VLCFA and total lipid contents; a pathway summarizing this interaction was depicted.. The results provide new insight into the mechanism by which EgMYB108 regulates lipid and VLCFA accumulation in oil palm.


Asunto(s)
Arecaceae , Arecaceae/genética , Arecaceae/metabolismo , Ácidos Grasos/metabolismo , Frutas/genética , Frutas/metabolismo , Aceite de Palma/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triglicéridos/metabolismo
11.
Langmuir ; 37(41): 12234-12241, 2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34617778

RESUMEN

The evaporation of a nano-suspension droplet on a substrate has gained extensive attention recently due to its potential application in the rising industry of functional coating. In this paper, we reported that the droplet evaporation behavior can be controlled by the nanoparticles' concentration and the functional group on the surface of nanoparticles. Experimental results indicated that the suspension of nanoparticles notably enhanced the evaporation rate of droplets and decreased the duration time of the continuous-contact-radius (CCR) stage. This effect was more obvious when the nanoparticles were modified by the perfluorodecyltrimethoxysilane (PDTS), which made the particles more hydrophobic. Besides, the modified nanoparticles can effectively inhibit the formation of coffee rings during evaporation. These results may have important applications for the energy-efficient enhancement of the water evaporation rate.

12.
Chem Pharm Bull (Tokyo) ; 69(1): 59-66, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33087641

RESUMEN

Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.


Asunto(s)
Berberina/farmacología , Descubrimiento de Drogas , Hipolipemiantes/farmacología , Lípidos/antagonistas & inhibidores , Células 3T3 , Animales , Berberina/análogos & derivados , Berberina/química , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Hipolipemiantes/síntesis química , Hipolipemiantes/química , Ratones , Estructura Molecular
13.
J Cell Mol Med ; 24(24): 14270-14279, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33145962

RESUMEN

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few studies have focused on the changes of NK, T- and B-cell subsets, inflammatory cytokines and virus-specific antibodies in patients with moderate COVID-19. A total of 11 RT-PCR-confirmed convalescent patients with COVID-19 and 11 patients with non-SARS-CoV-2 pneumonia (control patients) were enrolled in this study. NK, CD8+ T, CD4+ T, Tfh-like and B-cell subsets were analysed using flow cytometry. Cytokines and SARS-CoV-2-specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID-19 than in control patients (P = 0.017). Effector memory CD8+ T-cell counts significantly increased in patients with COVID-19 during a convalescent period of 1 week (P = 0.041). TIM-3+ Tfh-like cell and CD226+ Tfh-like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS+ Tfh-like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS-CoV-2. The increase in effector memory CD8+ T-cell counts, the up-regulation of inhibitory molecules and the down-regulation of active molecules on CD4+ T cells and Tfh-like cells in patients with COVID-19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID-19.


Asunto(s)
Anticuerpos Antivirales/biosíntesis , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , Citocinas/biosíntesis , Células Asesinas Naturales/inmunología , SARS-CoV-2/inmunología , Células T Auxiliares Foliculares/inmunología , Adulto , Anciano , Anticuerpos Antivirales/inmunología , Linfocitos T CD4-Positivos/inmunología , COVID-19/epidemiología , China/epidemiología , Citocinas/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
14.
Plant Cell Rep ; 39(11): 1505-1516, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32804247

RESUMEN

KEY MESSAGE: EgMADS21 regulates PUFA accumulation in oil palm. Oil palm (Elaeis guineensis Jacq.) is the most productive world oil crop, accounting for 36% of world plant oil production. However, the molecular mechanism of the transcriptional regulation of fatty acid accumulation and lipid synthesis in the mesocarp of oil palm by up- or downregulating the expression of genes involved in related pathways remains largely unknown. Here, an oil palm MADS-box gene, EgMADS21, was screened in a yeast one-hybrid assay using the EgDGAT2 promoter sequence as bait. EgMADS21 is preferentially expressed in early mesocarp developmental stages in oil palm fruit and presents a negative correlation with EgDGAT2 expression. The direct binding of EgMADS21 to the EgDGAT2 promoter was confirmed by electrophoretic mobility shift assay. Subsequently, transient expression of EgMADS21 in oil palm protoplasts revealed that EgMADS21 not only binds to the EgDGAT2 promoter but also negatively regulates the expression of EgDGAT2. Furthermore, EgMADS21 was stably overexpressed in transgenic oil palm embryoids by Agrobacterium-mediated transformation. In three independent transgenic lines, EgDGAT2 expression was significantly suppressed by the expression of EgMADS21. The content of linoleic acid (C18:2) in the three transgenic embryoids was significantly decreased, while that of oleic acid (C18:1) was significantly increased. Combined with the substrate preference of EgDGAT2 identified in previous research, the results demonstrate the molecular mechanism by which EgMADS21 regulates EgDGAT2 expression and ultimately affects fatty acid accumulation in the mesocarp of oil palm.


Asunto(s)
Arecaceae/genética , Arecaceae/metabolismo , Ácidos Grasos Insaturados/metabolismo , Proteínas de Plantas/genética , Diacilglicerol O-Acetiltransferasa/genética , Diacilglicerol O-Acetiltransferasa/metabolismo , Ácidos Grasos Insaturados/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Aceite de Palma/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Protoplastos/metabolismo
15.
J Enzyme Inhib Med Chem ; 34(1): 955-972, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31072147

RESUMEN

In this article, a series of novel quinoline derivatives of ursolic acid (UA) bearing hydrazide, oxadiazole, or thiadiazole moieties were designed, synthesised, and screened for their in vitro antiproliferative activities against three cancer cell lines (MDA-MB-231, HeLa, and SMMC-7721). A number of compounds showed significant activity against at least one cell line. Among them, compound 4d exhibited the most potent activity against three cancer cell lines with IC50 values of 0.12 ± 0.01, 0.08 ± 0.01, and 0.34 ± 0.03 µM, respectively. In particular, compound 4d could induce the apoptosis of HeLa cells, arrest cell cycle at the G0/G1 phase, elevate intracellular reactive oxygen species level, and decrease mitochondrial membrane potential. In addition, compound 4d could significantly inhibit MEK1 kinase activity and impede Ras/Raf/MEK/ERK transduction pathway. Therefore, compound 4d may be a potential anticancer agent and a promising lead worthy of further investigation.


Asunto(s)
Antineoplásicos/farmacología , MAP Quinasa Quinasa 1/antagonistas & inhibidores , Oxadiazoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Quinolinas/farmacología , Tiadiazoles/farmacología , Triterpenos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , MAP Quinasa Quinasa 1/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Modelos Moleculares , Estructura Molecular , Oxadiazoles/química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Quinolinas/química , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Tiadiazoles/química , Triterpenos/química , Ácido Ursólico
16.
Chem Pharm Bull (Tokyo) ; 67(9): 1006-1014, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31474723

RESUMEN

Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.


Asunto(s)
Ácido Clorogénico/química , Óxido Nítrico/metabolismo , Ácido Salicílico/química , Células A549 , Animales , Sitios de Unión , Supervivencia Celular/efectos de los fármacos , Ácido Clorogénico/farmacología , Humanos , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , PPAR gamma/química , PPAR gamma/metabolismo , Estructura Terciaria de Proteína , Células RAW 264.7
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 367-372, 2019 May.
Artículo en Zh | MEDLINE | ID: mdl-31631605

RESUMEN

OBJECTIVE: To determine the clinical epidemiological characteristics of newly reported human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)in southwestern China from 2001 to 2017. METHODS: Clinical data of newly diagnosed HIV/AIDS from 2001 to 2017 in the West China Hospital of Sichuan University were reviewed and analyze. RESULTS: A total of 1 520 228 patients were screened for HIV, including 285 983 outpatient and emergency patients and 1 234 245 inpatients. About 4 037 (0.27%) patients were confirmed with HIV/AIDS. The confirmation rate increased from 2001 to 2013, followed by a slight decline from 2014 to 2017. The male to female sex ratio of confirmed HIV/AIDS was 3.49:1 from 2001 to 2017, ranging from 1.65:1 to 5.08:1. The majority of patients were identified as Han (88.23%), had low education (58.66%), and married (54.75%). Peasants/herdsman comprised 26.33% of the patients. The proportion of young (15-29 years old), and middle-aged (≥50 years old) patients and those who were unmarried and had high education (senior high school and above) increased over time. Heterosexual transmission remained stable at about 60% while homosexual transmission increased by about 15% ( χ 2=14.436, P<0.005) since 2008. Transmissions through drug abuse( χ 2=71.633, P<0.005) and blood( χ 2=16.672, P<0.005) decreased. Of the 899 female newly reported HIV/ADIS patients, 77.20% were infected through heterosexual relationship. In comparison, of the 3 138 male patients, 61.41% were infected through heterosexual and 18.10% through homosexual relationships. Homosexual transmissions decreased with age, but heterosexual transmissions increased with age. Mother-to-child transmissions were concentrated in those between 0 and 15 years old (100%). CONCLUSION: Newly diagnosed HIV/AIDS cases increased over the years in the West China Hospital of Sichuan University, in particular in those of young and middle-aged, highly educated and unmarried. Heterosexual transmissions remain the main route.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , Infecciones por VIH/epidemiología , Síndrome de Inmunodeficiencia Adquirida/transmisión , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , China/epidemiología , Femenino , Infecciones por VIH/transmisión , Hospitales Generales , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Persona de Mediana Edad , Distribución por Sexo , Adulto Joven
18.
Opt Express ; 26(18): 22793-22800, 2018 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-30184934

RESUMEN

Quantum key distribution with polarized qubits has not yet been realized over the aerial fiber, due to rapid polarization changes. Here, we report our recent work towards quantum communication through an aerial fiber channel. We designed a fast polarization feedback module featuring high efficiency, fast speed, and good stability. With this module, we implemented long-distance quantum key distribution over different types of aerial fiber links based on polarization encoding. Our work takes a significant step towards the application of quantum communications in complex environments.

19.
Bioorg Med Chem ; 26(2): 356-365, 2018 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-29254892

RESUMEN

The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed.


Asunto(s)
N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Leucemia/tratamiento farmacológico , Proteína de la Leucemia Mieloide-Linfoide/antagonistas & inhibidores , Proteínas de Neoplasias/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , N-Metiltransferasa de Histona-Lisina/química , Humanos , Leucemia/genética , Estructura Molecular , Proteína de la Leucemia Mieloide-Linfoide/química , Proteínas de Neoplasias/química , Unión Proteica/efectos de los fármacos , Relación Estructura-Actividad
20.
Bioorg Chem ; 76: 380-385, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29241110

RESUMEN

WDR5, a subunit of the SET/MLL complex, plays critical roles in various biological progresses and are abnormally expressed in many cancers. Here we report the design, synthesis, and biochemical characterization of a new chemical tool to capture WDR5 protein. The probe is a biotinylated version of compound 30 that is a potent WDR5 inhibitor we previously reported. Importantly, the probe displayed high affinity to WDR5 protein in vitro binding potency and showed the ability in specifically and real time monitoring WDR5 protein. Further, the biotinylated tag of the probe enabled selectively "chemoprecipitation" of WDR5 from whole cell lysates of MV4-11. This probe provided a new approach to identify the overexpressed WDR5 protein in different cancer cells and applications to proteomic analysis of WDR5 and WDR5-binding partners.


Asunto(s)
Anilidas/farmacología , Benzamidas/farmacología , Biotina/análogos & derivados , Biotina/farmacología , N-Metiltransferasa de Histona-Lisina/metabolismo , Sondas Moleculares/farmacología , Anilidas/síntesis química , Benzamidas/síntesis química , Biotina/síntesis química , Línea Celular Tumoral , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Humanos , Péptidos y Proteínas de Señalización Intracelular , Simulación del Acoplamiento Molecular , Sondas Moleculares/síntesis química , Unión Proteica
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