RESUMO
Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease that has been linked to gut microbiome dysbiosis. Therefore, this study aims to investigate the effects of Akkermansia muciniphila (Am) on AAA mice and the biomolecules involved. AAA mice were generated using angiotensin II (Ang II), and 16sRNA sequencing was used to identify an altered abundance of microbiota in the feces of AAA mice. Vascular smooth muscle cell (VSMC) markers and apoptosis, and macrophage infiltration in mouse aortic tissues were examined. The abundance of Am was reduced in AAA mouse feces, and endothelial PAS domain-containing protein 1 (EPAS1) was downregulated in AAA mice and VSMC induced with Ang II. Am delayed AAA progression in mice, which was blunted by knockdown of EPAS1. EPAS1 was bound to the Cbp/p300-interacting transactivator 2 (CITED2) promoter and promoted CITED2 transcription. CITED2 reduced VSMC apoptosis and delayed AAA progression. Moreover, EPAS1 inhibited macrophage inflammatory response by promoting CITED2 transcription. In conclusion, gut microbiome dysbiosis in AAA induces EPAS1-mediated dysregulation of CITED2 to promote macrophage inflammatory response and VSMC apoptosis.
Assuntos
Akkermansia , Aneurisma da Aorta Abdominal , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Microbioma Gastrointestinal , Transativadores , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Aneurisma da Aorta Abdominal/microbiologia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Camundongos , Transativadores/metabolismo , Transativadores/genética , Masculino , Modelos Animais de Doenças , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/microbiologia , Músculo Liso Vascular/patologia , Apoptose , Angiotensina II/metabolismo , Miócitos de Músculo Liso/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Disbiose/microbiologiaRESUMO
Morphology and function in a fetal heart with severe tricuspid regurgitation remains challenging. The aim of this study was to assess cardiac morphology and function in fetuses with severe tricuspid regurgitation by fetal heart quantification (HQ) and to assess the practical value of fetal HQ. Clinical information was analyzed for 63 pregnant women who underwent fetal cardiac ultrasonography. The women were divided into those who had a fetus with severe tricuspid regurgitation (n = 20) and those with a normal fetus (n = 40). The global sphericity index (GSI), fractional area change (FAC), and global longitudinal strain (GLS) of both ventricles and the sphericity index (SI) and fractional shortening (FS) of 24 segments were quantified by fetal HQ using speckle tracking imaging. Fetuses with severe tricuspid regurgitation had a significantly lower GSI (1.14 ± 0.10 vs. 1.26 ± 0.08, p < 0.001) and a higher GSI Z-score (-0.98 ± 1.01 vs. 0.25 ± 0.87, p < 0.001) as well as a significantly lower right ventricular FAC (36.50 ± 7.34% vs. 45.19 ± 3.39%, p < 0.001), FAC Z-score (-1.02 ± 1.41 vs. 0.49 ± 0.74, p < 0.001), and GLS (-21.01 ± 5.66% vs. 45.19 ± 3.49%, p < 0.001). The SI and SI Z-score were significantly lower in segments 1-18 of the right ventricle in fetuses with severe tricuspid regurgitation (p < 0.05); furthermore, FS of segments 1-12 and 19-24 and the FS Z-score of segments 18-24 were significantly lower in fetuses with severe tricuspid regurgitation (p < 0.05). Fetal HQ is useful for evaluation of cardiac morphology and function in fetuses with severe tricuspid regurgitation and can provide important reference information for both clinical diagnosis and treatment.
Assuntos
Insuficiência da Valva Tricúspide , Humanos , Feminino , Gravidez , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Ventrículos do Coração , Ultrassonografia Pré-Natal/métodosRESUMO
The torque is a significant indicator reflecting the comprehensive operational characteristics of a power system. Thus, accurate torque measurement plays a pivotal role in ensuring the safety and stability of the system. However, conventional torque measurement systems predominantly rely on strain gauges adhered to the shaft, often leading to reduced accuracy, poor repeatability, and non-traceability due to the influence of strain gauge adhesion. To tackle the challenge, this paper introduces a photoelectric torque measurement system. Quadrants of photoelectric sensors are employed to capture minute deformations induced by torque on the rotational axis, converting them into measurable voltage. Subsequently, the system employs the radial basis function neural network optimized by simulated annealing combined with particle swarm algorithm (SAPSO-RBF) to establish a correlation between measured torque values and standard references, thereby calibrating the measured values. Experimental results affirm the system's capability to accurately determine torque measurements and execute calibration, minimizing measurement errors to 0.92%.
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The COVID-19 pandemic, caused by SARS-CoV-2, has led to over 750 million infections and 6.8 million deaths worldwide since late 2019. Due to the continuous evolution of SARS-CoV-2, many significant variants have emerged, creating ongoing challenges to the prevention and treatment of the pandemic. Therefore, the study of antibody responses against SARS-CoV-2 is essential for the development of vaccines and therapeutics. Here we perform single particle cryo-electron microscopy (cryo-EM) structure determination of a rabbit monoclonal antibody (RmAb) 9H1 in complex with the SARS-CoV-2 wild-type (WT) spike trimer. Our structural analysis shows that 9H1 interacts with the receptor-binding motif (RBM) region of the receptor-binding domain (RBD) on the spike protein and by directly competing with angiotensin-converting enzyme 2 (ACE2), it blocks the binding of the virus to the receptor and achieves neutralization. Our findings suggest that utilizing rabbit-derived mAbs provides valuable insights into the molecular interactions between neutralizing antibodies and spike proteins and may also facilitate the development of therapeutic antibodies and expand the antibody library.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Anticorpos Monoclonais , Pandemias , Microscopia Crioeletrônica , Anticorpos Antivirais , Receptores Virais/metabolismo , Anticorpos Neutralizantes , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/químicaRESUMO
Sensing sponge materials with light weight, high elasticity, and electrical sensing properties are in enormous demand in electronic fields, but there is an imminent need to develop a scalable and facile method for the manufacture of the sensing material. Herein, an efficient in situ polymerization and convenient preparation process is reported to manufacture the microporous liquid metal/carbon nanotube-polysulfide rubber (LM/CNT-PSR) sponges with excellent mechanical and electrical properties, based on fluidic LMs and rigid CNTs with unique synergistic effect for sponge composites. Excellent mechanical properties of LM/CNT-PSR sponges, such as low density, excellent elasticity, remarkable mechanical recoverability, and self-healing property, are endowed by the interconnected microporous structure of sponge and flexible polysulfide rubber matrix with disulfide bonds. In addition, the synergistic effect of LMs and CNTs leads to excellent conductivity and unique electrical sensing property under mechanical pressure. Microporous LM/CNT-PSR sponges with high performance and simple fabrication process are promising sensing materials for various electronic devices, such as human motion monitoring, and weighing sensing.
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Nanotubos de Carbono , Polímeros , Humanos , Polímeros/química , Nanotubos de Carbono/química , Borracha , MetaisRESUMO
In this study, we designed and developed a DOX nanodrug delivery system (PEG-GA@ZIF-8@DOX) using ZIF-8 as the carrier and glycyrrhetinic acid (GA) as the targeting ligand. We confirmed that DOX was loaded and PEG-GA was successfully modified on the surface of the nanoparticles. The in vitro release profile of the system was investigated at pH 5.0 and 7.4. The cellular uptake, in vitro cytotoxicity, and lysosomal escape characteristics were examined using HepG2 cells. We established an H22 tumor-bearing mouse model and evaluated the in vivo antitumor activity. The results showed that the system had a uniform nanomorphology. The drug loading capacity was 11.22 ± 0.87%. In acidic conditions (pH 5.0), the final release rate of DOX was 57.73%, while at pH 7.4, it was 25.12%. GA-mediated targeting facilitated the uptake of DOX by the HepG2 cells. PEG-GA@ZIF-8@DOX could escape from the lysosomes and release the drug in the cytoplasm, thus exerting its antitumor effect. When the in vivo efficacy was analyzed, we found that the tumor inhibition rate of PEG-GA@ZIF-8@DOX was 67.64%; it also alleviated the loss of the body weight of the treated mice. This drug delivery system significantly enhanced the antitumor effect of doxorubicin in vitro and in vivo, while mitigating its toxic side effects.
Assuntos
Ácido Glicirretínico , Neoplasias Hepáticas , Camundongos , Animais , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Sistemas de Liberação de Medicamentos/métodosRESUMO
A cladding-pumped 4-core erbium-doped fiber (4C-EDF) with a pedestal structure has been firstly, to the best of our knowledge, proposed and fabricated for space division multiplexing (SDM) amplification. The numerical simulation shows that the index-raised pedestal around the fiber core can improve power conversion efficiency (PCE) by enhancing pump power usage. Compared with conventional 4C-EDF, the 4C-EDF with a pedestal has a gain improvement of 4.5 dB and a PCE enhancement of 91.8%, according to the experimental results (pedestal fiber: 9.55%, conventional fiber: 4.98%). For a 6 dBm total input signal power at L-band and a 7.8 W pump power at 976 nm, the pedestal 4C-EDF shows an average gain of 25 dB and an average noise figure (NF) of 6.5 dB over all cores in the wavelength range of 1570.41 nm to 1610.87 nm. The core-to-core gain variation is less than 2 dB.
RESUMO
Spatial division multiplexing (SDM) is one of the most important technologies that may help to solve the future capacity crisis. However, to date, SDM optical amplification is still a challenge for its application. Herein, we numerically and experimentally demonstrated a few-mode Er/Yb co-doped fiber amplifier (FM-EYDFA) for extended L-band operation. A double cladding Er/Yb co-doped fiber was fabricated to expand the L-band bandwidth and a novel, to the best of our knowledge, cladding-pumped pseudo-two-stage amplification configuration was proposed to enhance the L-band gain. With an initial signal power of -16.8 dBm and an injected pump power of 8.8 W at 940â nm, the 20-dB gain range was covered to 1620â nm for two-mode groups of LP01 and LP11. Importantly, the average gain of 25â dB and average differential modal gain (DMG) of <1â dB were obtained in the wavelength range of 1570-1620â nm for all modes. Our results suggest that the cladding-pumped pseudo-two-stage amplifier based on Er/Yb co-doped fiber providing low DMG, and broad bandwidth has a great potential for increasing the future SDM capacity.
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Dihydromyricetin (DHM) has garnered attention due to its promising antitumor activity, but its low bioavailability restricts its clinical application. Thus, developing nano-drug delivery systems could enhance its antitumor activity. We prepared DHM@ZIF-8 nanoparticles using the zeolite imidazole framework-8 (ZIF-8) as a carrier loaded with dihydromyricetin. A series of characterizations were performed, including morphology, particle size, zeta potential, X-single crystal diffraction, ultraviolet spectroscopy, infrared spectroscopy, and Brunauer-Emmett-Teller (BET). The in vitro release characteristics of DHM@ZIF-8 under pH = 5.0 and pH = 7.4 were studied using membrane dialysis. The antitumor activity and pro-apoptotic mechanism of DHM@ZIF-8 were investigated through CCK-8 assay, reactive oxygen species (ROS), Annexin V/PI double-staining, transmission electron microscopy, and Western blot. The results depicted that DHM@ZIF-8 possessed a regular morphology with a particle size of 211.07 ± 9.65 nm (PDI: 0.19 ± 0.06) and a Zeta potential of -28.77 ± 0.67 mV. The 24 h drug releasing rate in PBS solution at pH = 7.4 was 32.08% and at pH = 5.0 was 85.52% in a simulated tumor micro acid environment. DHM@ZIF-8 could significantly enhance the killing effect on HepG2 cells compared to the prodrug. It can effectively remove ROS from the tumor cells, promote apoptosis, and significantly affect the expression of apoptosis-related proteins within tumor cells.
Assuntos
Zeolitas , Flavonóis , Células Hep G2 , Humanos , Espécies Reativas de Oxigênio/metabolismo , Diálise Renal , Zeolitas/química , Zeolitas/farmacologiaRESUMO
2D bismuth nanosheets are a promising layered material for formate-producing via electrocatalytic CO2 conversion. However, the commercial interest of bismuth nanosheets in CO2 electroreduction is still rare due to the undesirable current density for formate at moderate operation potentials (about 200 mA mg-1 ) and harsh synthesis conditions (high temperature and/or high pressure). This work reports the preparation of Bi nanosheets with a lateral size in micrometer-scale via electrochemical cathodic exfoliation in aqueous solution at normal pressure and temperature. As-prepared Bi LNSs (L indicates large lateral size) possess high Faradaic efficiencies over 90% within a broad potential window from -0.44 to -1.10 V versus RHE and a superior partial current density about 590 mA mg-1 for formate in comparison with state-of-the-art results. Structure analysis, electrochemical results, and density functional theory calculations demonstrate that the increasing tensile lattice strain observed in Bi LNSs leads to less overlap of d orbitals and a narrower d-band width, which tuning the intermediate binding energies, and therefore promotes the intrinsic activity.
RESUMO
The gain bandwidth of the erbium-doped fiber amplifier limits the enhancement of the transmission capacity in optical fiber communication systems. This Letter reports an erbium-ytterbium co-doped phosphosilicate fiber, which is expected to increase transmission capacity by extending the L-band gain bandwidth to 1623 nm. The fiber was fabricated by modified chemical vapor deposition combined with solution doping technology. The mechanism of bandwidth-expansion by inhibiting the signal excited-state absorption was investigated. When the signal power and pump power were maintained at -3.7dBm and â¼720mW at 1480 nm, the 20 dB gain range was extended out to 1623 nm. Additionally, the noise figure at 1623 nm decreased to 6.01 dB, with 23 dBm saturated output power. The results show that the erbium-ytterbium co-doped phosphosilicate fiber has a great potential for extending L-band amplification.
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The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin α4ß7, a gut-homing receptor. Using both cell-surface expressed α4ß7 and a soluble α4ß7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of α4ß7 in a cation -sensitive manner and is inhibited by soluble MAdCAM. Thus, V2 mimics MAdCAM in the way that it binds to α4ß7, providing HIV a potential mechanism to discriminate between functionally distinct subsets of lymphocytes, including those with gut-homing potential. Furthermore, α4ß7 antagonists developed for the treatment of inflammatory bowel diseases, block V2 binding to α4ß7. A 15-amino acid V2 -derived peptide is sufficient to mediate binding to α4ß7. It includes the canonical LDV/I α4ß7 binding site, a cryptic epitope that lies 7-9 amino acids amino terminal to the LDV/I, and residues K169 and I181. These two residues were identified in a sieve analysis of the RV144 vaccine trial as sites of vaccine -mediated immune pressure. HIV and SIV V2 mAbs elicited by both vaccination and infection that recognize this peptide block V2-α4ß7 interactions. These mAbs recognize conformations absent from the ß- barrel presented in a stabilized HIV SOSIP gp120/41 trimer. The mimicry of MAdCAM-α4ß7 interactions by V2 may influence early events in HIV infection, particularly the rapid seeding of gut tissues, and supports the view that HIV replication in gut tissue is a central feature of HIV pathogenesis.
Assuntos
Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/prevenção & controle , Integrinas/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vacinas contra a AIDS/química , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/metabolismo , Animais , Anticorpos Monoclonais , Sítios de Ligação/imunologia , Linhagem Celular Tumoral , Epitopos/química , Epitopos/imunologia , Anticorpos Anti-HIV/química , Anticorpos Anti-HIV/imunologia , Anticorpos Anti-HIV/metabolismo , Infecções por HIV/imunologia , HIV-1/imunologia , Macaca , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas/imunologia , Vacinas contra a SAIDS/química , Vacinas contra a SAIDS/imunologia , Vacinas contra a SAIDS/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vacinação/métodosRESUMO
Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague-Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1ß, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.
Assuntos
Antioxidantes/metabolismo , Aorta Torácica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Triterpenos/farmacologia , Animais , Aorta Torácica/metabolismo , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Triterpenos Pentacíclicos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido BetulínicoRESUMO
OBJECTIVE: To explore and analyze the effect of liquid dressing in relieving pain and preventing incision adhesion after circumcision and its clinical application value. METHODS: Ninety male patients underwent circumcision in Hangzhou Third People's Hospital from September to November 2019, with the incision covered with liquid dressing + vaseline gauze (group A, n = 30), liquid dressing alone (group B, n = 30) or vaseline gauze only (group C, n = 30). At 2, 4 and 6 days after surgery, we compared the Visual Analogue Scale (VAS) pain intensity at dressing change, incision bleeding after dressing removal and incidence of postoperative complications among the three groups of patients. RESULTS: At 2, 4 and 6 days after surgery, the VAS pain score and incidence of incision bleeding were significantly lower in groups A and B than in C (P < 0.05). At 2 days, both the VAS pain score and incidence of incision bleeding were markedly decreased in group A as compared with those in group B (P < 0.05). At 4 and 6 days, the VAS pain score remained lower in group A than in B (P < 0.05), but the incidence rate of incision bleeding showed no significant difference between the two groups (P > 0.05). No statistically significant differences were observed in the incidence of postoperative complications among the three groups (P > 0.05). CONCLUSIONS: Liquid dressing can reduce pain intensity at dressing change, prevent incision adhesion and consequent dressing change-induced tearing and bleeding, and therefore promote incision healing after circumcision. Its combination with vaseline gauze can achieve an even better effect.
Assuntos
Bandagens/classificação , Circuncisão Masculina , Cicatrização , Humanos , Masculino , Dor/prevenção & controle , Medição da DorRESUMO
Selective hydrogenation of unsaturated aldehydes to unsaturated alcohols is a valuable but challenging task for synthesizing fine chemicals. We report that single Rh atoms anchored to the edges of 2D MoS2 sheets can efficiently convert crotonaldehyde to crotyl alcohol with 100% selectivity via a steric confinement effect of pocketlike active sites. Characterization results suggest that the synthesized Rh1/MoS2 single-atom catalysts (SACs) possess a unique geometric and electronic configuration, which confines the adsorption mode of the reactant molecule by a steric effect. The DFT calculations suggest that the MoS2 sheets terminate with oxidized Mo edges and the Rh1 stably anchors at the Mo cation vacancy site, which can facilely dissociate H2 to H atoms. The dissociated H atoms spill over to react with the edge O atoms to form OH species and create an HO-Mo-Rh1-Mo-OH configuration, resembling a pocketlike active site, which confines the adsorption mode of the crotonaldehyde due to steric effects. Such specific adsorption configuration yields 100% selectivity. The strategy of constructing pocketlike active centers with single metal atoms and 2D nanosheets opens new approaches to designing highly selective SACs for specific classes of catalytic transformations.
RESUMO
Q-switching operation based on stimulated Brillouin scattering (SBS) has been developed for decades due to its inexpensive configuration, high pulse energy output, and the potential to be free from wavelength and material limitations. However, unstable and uncontrollable pulse output affected by SBS's stochastic nature hinders its development. In this work, we demonstrated a unique robust SBS-based Q-switched all-fiber laser. Firstly, a numerical model is developed and a general analysis about the robust Q-switching mechanism is presented. Simulation results show that the spectrum modulation effect such as FP interference is efficient for system to realize steady and controllable output. Secondly, we incorporated a Fabry-Perot (FP) interferometer made of two un-contact end faces of fiber connectors into a SBS-based Q-switched system and demonstrated passively robust Q-switching with simpler and cheaper configuration than most reported ones. Under 600 mW pump power, the SNR was measured to be as high as 62.96 dB, which is the highest SNR obtained from SBS-based Q-switched lasers. To our best knowledge, this is the first demonstration of robust SBS-based Q-switching without any external measures.
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Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) µmol·L-1.
Assuntos
Broussonetia/química , Flavonoides/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
Small supernumerary ring chromosome 6 (sSRC[6]) is a rare chromosomal abnormality characterized by a broad clinical phenotype. The spectrum of this disorder can range from phenotypically normal to severe developmental delay and congenital anomalies. We describe two unrelated patients with small SRCs derived from chromosome 6 with a novel bone phenotype. Both patients presented with a complex bone disorder characterized by severe osteopenia, pathologic fractures, and cyst-like lesions within the bone. Imaging revealed decreased bone mineral density, mutiple multiloculated cysts and cortical thinning. Lesion pathology in both patients demonstrated a bland cyst wall with woven dysplastic appearing bone entrapped within it. In patient 1, array comparative genomic hybridization (CGH) detected a tandem duplication of region 6p12.3 to 6q12 per marker chromosome. Cytogenetic analysis further revealed a complex patient of mosaicism with some cell lines displaying either one or two copies of the marker indicative of both tetrasomy and hexasomy of this region. Patient 2 was mosaic for a sSRC that encompassed a 26.8 Mb gain from 6p21.2 to 6q12. We performed an in-depth clinical analysis of a phenotype not previously observed in sSRC(6) patients and discuss the potential influence of genes located within this region on the skeletal presentation observed.
Assuntos
Cistos Ósseos Aneurismáticos/genética , Transtornos Cromossômicos/genética , Fraturas Espontâneas/genética , Osteocondrodisplasias/genética , Adolescente , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Bandeamento Cromossômico , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 6/genética , Hibridização Genômica Comparativa , Análise Citogenética , Fraturas Espontâneas/diagnóstico por imagem , Marcadores Genéticos/genética , Humanos , Cariotipagem , Masculino , Mosaicismo , Osteocondrodisplasias/diagnóstico por imagem , Fenótipo , Cromossomos em AnelRESUMO
LC-MS-guided phytochemical isolation of malonylginsenosides, featuring neutral elimination of CO2 and C3H2O3 by the negative mode collision-induced dissociation, from the flower buds of Panax ginseng led to the isolation of 19 malonyl-substituted triterpenoid saponins. They include 15 new malonylginsenosides, malonylfloralginsenosides-Re1-Re3 (1-3), -Rb1 and -Rb2 (4, 5), -Rd1-Rd6 (6-11), and -Rc1-Rc4 (12-15), and the known m-Rb1, m-Rc, m-Rb2, and m-Rd (16-19). Compound 11 represents the first dimalonyl saponin isolated from the Panax genus, while 2-4, 9, and 10 are five ginsenosides with single malonylation at the C-20 sugar chain. The antidiabetic activities of nine of these malonyl-substituted ginsenosides (1, 3, 4, 8, 13, and 16-19) and five of the corresponding non-malonyl ginsenosides (Re, Rb1, Rb2, Rc, and Rd) were evaluated by L6 myotubes' glucose consumption and AMPKα2ß1γ1 activation. Ginsenoside Rb2, 1, and 18 promoted glucose consumption of differentiated L6 myotubes, while ginsenosides Rb1, Rb2, and Rd and the malonylginsenosides 4, 8, 13, 16, 17, and 19 activated AMPKα2ß1γ1 (EC50: 0.0168-2.8 µM, fold: 1.7-4.7).
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Flores/química , Ginsenosídeos/isolamento & purificação , Ginsenosídeos/farmacologia , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Panax/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Animais , Cromatografia Líquida , Diabetes Mellitus/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/química , Hipoglicemiantes/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ratos , Saponinas/químicaRESUMO
During conventional ultrasound imaging, the need for multiple transmissions for one image and the time of flight for a desired imaging depth limit the frame rate of the system. Using a single plane wave pulse during each transmission followed by parallel receive processing allows for high frame rate imaging. However, image quality is degraded because of the lack of transmit focusing. Beamforming by spatial matched filtering (SMF) is a promising method which focuses ultrasonic energy using spatial filters constructed from the transmit-receive impulse response of the system. Studies by other researchers have shown that SMF beamforming can provide dynamic transmit-receive focusing throughout the field of view. In this paper, we apply SMF beamforming to plane wave transmissions (PWTs) to achieve both dynamic transmit-receive focusing at all imaging depths and high imaging frame rate (>5000 frames per second). We demonstrated the capability of the combined method (PWT + SMF) of achieving two-way focusing mathematically through analysis based on the narrowband Rayleigh-Sommerfeld diffraction theory. Moreover, the broadband performance of PWT + SMF was quantified in terms of lateral resolution and contrast from both computer simulations and experimental data. Results were compared between SMF beamforming and conventional delay-and-sum (DAS) beamforming in both simulations and experiments. At an imaging depth of 40 mm, simulation results showed a 29% lateral resolution improvement and a 160% contrast improvement with PWT + SMF. These improvements were 17% and 48% for experimental data with noise.