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Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.
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BACKGROUND: The picosecond alexandrite laser has been safely and effectively used to treat the nevus of Ota in adults. However, limited data are available for children. OBJECTIVE: To investigate the efficacy, safety, and correlative influencing factors of a 755nm picosecond alexandrite laser in the treatment of nevus of Ota in children. METHODS: We retrospectively analyzed Chinese children with nevus of Ota who received a 755nm picosecond alexandrite laser treatment in a tertiary dermatological hospital. RESULT: A total of 305 pediatric patients received an average of two treatments achieving an average of 79% pigment clearance. After the first treatment, 22 patients achieved complete clearance (95%-100%), and 72 patients achieved excellent response (75%-94%), with an average initial efficacy of 63% lesion clearance. Treatment at an early age achieved better initial efficacy (0- to 12-month group >1- to 6-year group, 6- to 12-year group). And 0- to 12-month group achieved better final efficacy. More treatment sessions also increased the final efficacy. Both initial efficacy and final efficacy were better when treating a darker lesion. The incidence of complications was 12.1%, with 10.8% being post-inflammatory hyperpigmentation and 1.3% being hypopigmentation. The rate of recurrence was 6.6%. LIMITATION: Retrospective study. CONCLUSION: A 755nm picosecond alexandrite laser is safe and effective in treating nevus of Ota in children. Younger to initiate treatment, darker lesions, and more treatments are positively associated with better pigmentation clearance.
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Láseres de Estado Sólido , Nevo de Ota , Neoplasias Cutáneas , Humanos , Nevo de Ota/radioterapia , Nevo de Ota/cirugía , Láseres de Estado Sólido/uso terapéutico , Niño , Estudios Retrospectivos , Femenino , Masculino , Preescolar , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Lactante , Adolescente , Resultado del Tratamiento , Recién Nacido , Terapia por Luz de Baja Intensidad/métodosRESUMEN
BACKGROUND: Various surgical techniques and conservative therapies are useful tools for treating proximal humerus fractures (PHFs), but it is important to understand how to properly utilize them. Therefore, we performed a systematic review and network meta-analysis to compare and rank the efficacy and safety of medical treatments for PHF. METHODS: PubMed, Embase, the Cochrane Library, and the ClinicalTrials.gov databases were systematically searched for eligible randomized controlled trials (RCTs) from inception until June 2022. Conservative therapy-controlled or head-to-head RCTs of open reduction internal fixation (ORIF), intramedullary nailing (IMN), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (RTSA) used for the treatment of adult patients with PHF were included. The surface under the cumulative ranking (SUCRA) probabilities were applied to compare and rank the effects of medical treatments for PHF. RESULTS: Eighteen RCTs involving 1,182 patients with PHF were selected for the final analysis. Mostly baseline characteristics among groups were well balanced, and the imbalanced factors only included age, injury type, medial comminution, blood loss, and cognitive function in single trial. The SUCRA probabilities found that RTSA provided the best effect on the Constant-Murley score (SUCRA: 100.0%), and the disabilities of the arm, shoulder and hand (DASH) score (SUCRA: 99.0%). Moreover, HA (SUCRA: 85.5%) and RTSA (SUCRA: 68.0%) had a relatively better effect on health-related quality of life than the other treatment modalities. Furthermore, conservative therapy (SUCRA: 84.3%) and RTSA (SUCRA: 80.7%) were associated with a lower risk of secondary surgery. Finally, the best effects on the risk of complications are varied, including infection was observed with conservative therapy (SUCRA: 94.2%); avascular necrosis was observed in HA (SUCRA: 78.1%), nonunion was observed in RTSA (SUCRA: 69.6%), and osteoarthritis was observed in HA (SUCRA: 93.9%). CONCLUSIONS: This study found that RTSA was associated with better functional outcomes, while the comparative outcomes of secondary surgery and complications varied. Optimal treatment for PHF should consider patient-specific factors.
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Artroplastía de Reemplazo de Hombro , Hemiartroplastia , Fracturas del Húmero , Fracturas del Hombro , Adulto , Humanos , Hemiartroplastia/efectos adversos , Fracturas del Húmero/cirugía , Húmero/cirugía , Metaanálisis en Red , Fracturas del Hombro/cirugía , Fracturas del Hombro/etiología , Resultado del TratamientoRESUMEN
Progesterone (PROG) and estrone (E1) are typical reproductive hormones in dairy cows. Assessing the levels of these hormones in vivo can aid in estrus identification. In the present work, the feasibility of the qualitative and quantitative detection of PROG and E1 using terahertz time-domain spectroscopy (THz-TDS) and metamaterial technology was preliminarily investigated. First, the time domain spectra, frequency domain spectra, and absorption coefficients of PROG and E1 samples were collected and analyzed. A vibration analysis was conducted using density functional theory (DFT). Subsequently, a double-ring (DR) metamaterial structure was designed and simulated using the frequency domain solution algorithm in CST Studio Suite (CST) software. This aimed to ensure that the double resonance peaks of DR were similar to the absorption peaks of PROG and E1. Finally, the response of DR to different concentrations of PROG/E1 was analyzed and quantitatively modeled. The results show that a qualitative analysis can be conducted by comparing the corresponding DR resonance peak changes in PROG and E1 samples at various concentrations. The best R2 for the PROG quantitative model was 0.9872, while for E1, it was 0.9828. This indicates that terahertz spectral-metamaterial technology for the qualitative and quantitative detection of the typical reproductive hormones PROG and E1 in dairy cows is feasible and worthy of in-depth exploration. This study provides a reference for the identification of dairy cow estrus.
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Estrona , Progesterona , Espectroscopía de Terahertz , Bovinos , Animales , Progesterona/análisis , Femenino , Espectroscopía de Terahertz/métodos , Estrona/análisis , Industria LecheraRESUMEN
The issue of hypersonic boundary layer transition prediction is a critical aerodynamic concern that must be addressed during the aerodynamic design process of high-speed vehicles. In this context, we propose an advanced mesoscopic method that couples the gas kinetic scheme (GKS) with the Langtry-Menter transition model, including its three high-speed modification methods, tailored for accurate predictions of high-speed transition flows. The new method incorporates the turbulent kinetic energy term into the Maxwellian velocity distribution function, and it couples the effects of high-speed modifications on turbulent kinetic energy within the computational framework of the GKS solver. This integration elevates both the transition model and its high-speed enhancements to the mesoscopic level, enhancing the method's predictive capability. The GKS-coupled mesoscopic method is validated through a series of test cases, including supersonic flat plate simulation, multiple hypersonic cone cases, the Hypersonic International Flight Research Experimentation (HIFiRE)-1 flight test, and the HIFiRE-5 case. The computational results obtained from these cases exhibit favorable agreement with experimental data. In comparison with the conventional Godunov method, the new approach encompasses a broader range of physical mechanisms, yielding computational results that closely align with the true physical phenomena and marking a notable elevation in computational fidelity and accuracy. This innovative method potentially satisfies the compelling demand for developing a precise and rapid method for predicting hypersonic boundary layer transition, which can be readily used in engineering applications.
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Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.
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We investigate to the best of our knowledge the first time the interactions of in-phase and out-of-phase Airy beams in Kerr, saturable and nonlocal nonlinear media with fourth-order diffraction using split-step Fourier transform method. Directly numerical simulations show that normal and anomalous fourth-order diffractions have profound effects on the interactions of the Airy beams in Kerr and saturable nonlinear media. We demonstrate the dynamics of the interactions in detail. In nonlocal media with fourth-order diffraction, nonlocality induces a long-range attractive force between Airy beams, leading to the formation of stable bound states of both in-phase and out-of-phase breathing Airy soliton pairs which are always repulsive in local media. Our results have potential applications in all-optical devices for communication and optical interconnects, etc.
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Photocatalysts with hollow structures have drawn great interest owing to their high specific surface area, which can enhance the photocatalytic performance. Herein, we designed the hollow cubic Cu2-xS@Ni-Mo-S nanocomposites by vulcanizing from the Cu2O template and loading the Ni-Mo-S lamellas. The Cu2-xS@Ni-Mo-S composites greatly improved the photocatalytic hydrogen performance. Among them, Cu2-xS-NiMo-5 achieved the optimal photocatalytic rate of 1326.07 µmol/g h, which is approximately 3.85 times higher than that of hollow Cu2-xS (344 µmol/g h) and had good stability for 16 h. The enhanced photocatalytic property was attributed to the metallic behavior of bimetallic Ni-Mo-S lamellas and the LSPR (localized surface plasmon resonance) effect of Cu2-xS. The bimetallic Ni-Mo-S can effectively capture the photogenerated electrons and quickly transfer-diffuse to produce H2. Meanwhile, the hollow Cu2-xS not only provided many more active sites to take part in the reaction but also introduced the LSPR effect to increase the solar utilization. This work provides valuable insights into the synergistic effect of using non-precious metal co-catalysts and the LSPR materials to assist in the photocatalytic hydrogen evolution.
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Solanum nigrum fruit is like a treasure house for anticancer drugs because of its steroidal alkaloids. However, the clinical treatment of cancer mainly uses immature fruits, which can cause a toxic reaction if eaten directly, while mature fruits are eaten as fruit. In order to clarify the reasons for the differences in pharmacodynamics and toxicity between them, we studied the composition and metabolism of steroidal alkaloids in fruits of different maturities based on liquid chromatography-tandem mass spectrometry and molecular networking. As a result, 114 steroidal glycoalkaloids were identified. During fruit ripening, the aglycones of steroidal alkaloids mainly undergo hydroxylation and carboxylation, and the sugar side chains mainly undergo acylation and glycosylation reactions. Furthermore, 219 steroidal alkaloids were identified in a metabolism experiment in rats. Metabolic processes include deglycosylation, redox, sulfuric acid binding, acetyl binding, and glucuronic acid-binding. Steroidal alkaloids in mature fruits have high molecular weight and polarity, which are difficult to absorb, and most of them are excreted through feces and urine, which may be the reason for their poor efficacy. This study lays a foundation for research on the biosynthesis of steroidal alkaloids and provides potential candidates for the discovery of new steroidal alkaloid anticancer drugs.
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Alcaloides , Solanum nigrum , Solanum , Ratas , Animales , Solanum nigrum/química , Frutas/química , Espectrometría de Masas en Tándem , Alcaloides/análisis , Esteroides/química , Cromatografía Liquida , Solanum/químicaRESUMEN
OBJECTIVE: The 730 nm picosecond titanium sapphire laser is a novel laser that shows promising results in treating freckles. This study aimed to further investigate the efficacy and safety of the 730 nm picosecond titanium sapphire laser for treating freckles in Asian patients compared with those of the 755 nm picosecond alexandrite laser. METHODS: Each face of 86 participants was split into two parts and randomly assigned either one session of 730 or 755 nm picosecond-laser treatment each. Efficacy and safety were determined based on blinded visual evaluations and self-reports at each follow-up visit. RESULTS: The treatment outcomes of the 730 nm picosecond laser for the treatment of freckles were comparable to those of the 755 nm picosecond laser, with 68.99 ± 7.42% and 69.27 ± 7.75% clearance, respectively (p > 0.05). Participants achieved similar Global Aesthetic Improvement Scale scores (4.04 ± 0.31 vs. 4.02 ± 0.30, respectively [p > 0.05]). Additionally, the 730 nm picosecond laser was perceived to be less painful than the 755 nm picosecond laser (4.69 ± 1.63 vs. 5.65 ± 1.80 nm, p < 0.0001). CONCLUSION: The 730 nm picosecond laser is safe and effective for the treatment of freckles in Asian patients. Besides, the 730 nm picosecond laser is less painful than the 755 nm picosecond laser.
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Láseres de Estado Sólido , Melanosis , Humanos , Láseres de Estado Sólido/uso terapéutico , Titanio , Resultado del Tratamiento , Dolor , Óxido de AluminioRESUMEN
Wetlands in the Yarlung Tsangpo River Basin (YTR) on the Qinghai-Tibet Plateau provide immense soil organic carbon (SOC) storage, which is highly susceptible to climate warming and requires urgent deciphering SOC stabilization mechanisms of long-term protection of SOC against decomposition. Conflicting views exist regarding whether persistent SOC is controlled by molecular features or by mineral protection. As such, this study quantified SOC stability using two thermal indices (TG-T50, and DSC), described molecular features of SOC using pyrolysis-gas chromatography-mass spectrometry, and measured SOC protection by minerals using a chemical extraction method. Results indicated SOC of topsoils had higher thermal stability, with TG-T50 and DSC-T50 of 337.61 °C and 384.58 °C, than that of subsoils with TG-T50 and DSC-T50 of 337.32 and 382.67 °C, respectively. We found subsoils had significantly higher proportions of aliphatic and aromatic compounds, while existed higher SOC associated with minerals. It seemed SOC stabilization differed with soil depths, in which mineral protection dictated SOC thermal stability in topsoils while molecular features posed a more important constraint on SOC stabilization in subsoils. Overall, our findings support the hypothesis of physical and chemical protection but emphasized that SOC thermal stability largely depended on to extent of the combination between molecular features and mineral protection, which explained 55% in topsoils and 73% in subsoils, respectively.
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Carbono , Suelo , Suelo/química , Carbono/análisis , Tibet , Humedales , Minerales/análisisRESUMEN
Considering the resistance and toxicity of traditional chemotherapeutic drugs, seeking potential candidate for treating breast cancer effectively is a clinical problem that should be solved urgently. Natural products have attracted extensive attention, owing to their multi-target advantages and low toxicity. In the current study, the effects of XK-81, a novel bromophenol compound extracted from Leathesia nana, on breast cancer, and its underlying mechanisms, were explored. Firstly, data from in vitro experiments indicated that 4T-1, one of common mouse breast cancer cell lines, was a XK-81-susceptible cell line, and ferroptosis was the major death manner in response to XK-81 treatment, which was evidenced by increasing intracellular Fe2+ and ROS level with condensed mitochondrial membrane densities, as well as decreasing the protein expressions of SLC7A11 and GPX4. In vivo, XK-81 suppressed the growth of 4T-1 breast-tumor in both BALB/C mice and zebrafish. Obviously, XK-81 decreased the protein expression of SLC7A11 and GPX4 in tumor tissues, hinting at the occurrence of ferroptosis. Moreover, XK-81 increased CD8+ T cells and NK cells numbers and regulated M1/M2 macrophage ratio in tumor tissues, indicating XK-81's immunotherapeutic effect. Additionally, the secretions of immune-related cytokines, including TNF-α, IL-1ß, and IL-12, were elevated with XK-81 stimulation in RAW 264.7 cells. Intriguingly, compared with doxorubicin-induced heart damage, XK-81 demonstrated the therapeutic advantage of little cardiotoxicity on the heart. XK-81 demonstrated potential antitumor advantage by both directly inducing ferroptosis-mediated death of tumor cells and immunization.
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Neoplasias Mamarias Animales , Pez Cebra , Ratones , Animales , Ratones Endogámicos BALB C , Inmunoterapia , InmunizaciónRESUMEN
The design and development of innovative multifunctional wound dressing materials in engineered biomaterials is essential for promoting tissue repair. In this study, nanofibrous wound dressing materials loaded with anti-inflammatory ingredients were manufactured by a promising electrospinning strategy, and their capability for treating diabetic wounds was also investigated. A scaffold blend consisting of an Enteromorpha polysaccharide and polyvinyl alcohol (PVA) was fabricated. The in vitro and in vivo studies confirmed the efficacy of PVA/EPP1 fiber. We found that PVA/EPP1 fiber accelerated the repair of a full-thickness skin wound in diabetic mice. The results suggest that this scaffold could effectively shorten the wound healing time by inhibiting inflammatory activity, which makes it a promising candidate for the treatment of hard-to-heal wounds caused by diabetes.
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Antiinflamatorios/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Polisacáridos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Diabetes Mellitus Experimental/complicaciones , Inflamación/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Polisacáridos/aislamiento & purificación , Alcohol Polivinílico/química , Algas Marinas/química , Factores de TiempoRESUMEN
Penthorum chinense Pursh. is a traditional herbal medicine of Miao, and its extracts (PCPE) have been used for treatment of liver diseases in the clinic including nonalcoholic fatty liver disease (NAFLD). However, the active components and pharmacological mechanisms of PCPE for treating NAFLD remain unclear. This study aimed to explore potential mechanisms of action through network pharmacology, molecular docking combined with experimental inâ vitro. A total of five dihydroflavonoids (1-5) with the same parent nucleus of pinocembrin (PCB) from PCPE, were selected as bioactive ingredients and 109 potential targets related to NAFLD were obtained from public databases and literature mining. The core targets related to the bile secretion signaling were selected based on PPI network and KEGG enrichment analysis for exploring the mechanism of PCPE against NAFLD. Molecular docking results showed good interaction between the core targets in bile secretion signaling pathway and the five compounds predicted to be bioactive. With the strong binding activity to retinoid X receptor-alpha (RXRA) and farnesoid X receptor (FXR) protein, pinocembrin-7-O-ß-D-glucoside (PCBG, the highest content in PCPE) and its metabolite PCB, could significantly increase the expression of RXRA, FXR and bile salt export pump (BSEP) in L02 cells, and significantly decrease the expression of cholesterol 7α-hydroxylase (CYP7A1) at mRNA and protein levels. This study provided favorable evidence for mechanism of the main dihydroflavonoids of PCPE against NAFLD, and presented a paradigm for the study of ethnomedicine.
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Enfermedad del Hígado Graso no Alcohólico , Ácidos y Sales Biliares , Humanos , Metabolismo de los Lípidos , Medicina Tradicional , Simulación del Acoplamiento Molecular , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológicoRESUMEN
In this study, keratins were extracted from pig nail waste through the reduction method using L-cysteine as a reductant. Curcumin was successively incorporated in a mixed solution including keratin, gelatin, and glycerin to prepare different kinds of keratin/gelatin/glycerin/curcumin composite films. The morphology of the keratin/ gelatin/glycerin/curcumin composite films were examined using scanning electron microscopy. The structures and the molecular interactions between curcumin, keratin, and pectin were examined using Fourier transform infrared spectroscopy and X-ray diffraction, and the thermal properties were determined through thermogravimetric analysis. The tensile strengths of keratin/gelatin/glycerin/curcumin and keratin/gelatin/curcumin composite films are 13.73 and 12.45 MPa, respectively, and their respective elongations at break are 56.7% and 4.6%. In addition, compared with the control group (no film wrapped on the surface of tomato), the ratio of weight loss of the keratin (7.0%)/gelatin (10%)/glycerin (2.0%)/curcumin (1.0%) experimental groups is 8.76 ± 0.2%, and the hardness value of the tomatoes wrapped with composite films is 11.2 ± 0.39 kg/cm3. Finally, the composite films have a superior antibacterial effect against Staphylococcus aureus and Escherichia coli because of the addition of curcumin. As the concentration of curcumin reaches 1.0%, the antibacterial activity effect of the film is significantly improved. The diameter of the inhibition zone of E. coli is (12.16 ± 0.53) mm, and that of S. aureus is (14.532 ± 0.97) mm. The multifunctional keratin/gelatin/glycerin/curcumin bioactive films have great potential application in the food packaging industry.
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Curcumina , Solanum lycopersicum , Animales , Antibacterianos/química , Antibacterianos/farmacología , Curcumina/química , Curcumina/farmacología , Cisteína/farmacología , Escherichia coli , Embalaje de Alimentos , Gelatina/química , Gelatina/farmacología , Glicerol/farmacología , Queratinas/química , Pectinas/farmacología , Sustancias Reductoras/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus , PorcinosRESUMEN
Magnoflorine is an important aporphine alkaloid in Coptidis Rhizoma. As reported previously, coexisting components in Coptidis Rhizoma can change the pharmacokinetic characteristics of magnoflorine. To illustrate the interactional links of magnoflorine with its coexisting components in Coptidis Rhizoma, the present study investigated the influence of coexisting components in Coptidis Rhizoma on the excretion of magnoflorine in rat bile, urine, and feces. The rats were dosed with magnoflorine(30 mg·kg~(-1)) and water decoction of Coptidis Rhizoma(equivalent to 30 mg·kg~(-1) magnoflorine) via intragastric administration, and magnoflorine(10 mg·kg~(-1)) by intravenous administration, respectively, and the excretion of magnoflorine in rat bile, urine, and feces in 24 h was observed. The excretion rates of magnoflorine in bile and urine in 24 h were 0.90% and 37.11% respectively after intravenous administration of magnoflorine, which suggested that urination was the main excretive way of magnoflorine. The excretion rates of magnoflorine in feces were 8.77% and 6.18% respectively after intragastric administration of magnoflorine and water decoction of Coptidis Rhizoma, which indicated that defecation was the main excretion route of magnoflorine. The cumulative excretion rates of magnoflorine in the bile, urine, and feces in the Coptidis Rhizoma water decoction group were 77.78%, 79.44%, and 70.47% of those in the magnoflorine group. The results showed that the cumulative excretion rates of magnoflorine in rat bile, urine, and feces were not high, suggesting that magnoflorine was metabolized significantly in rats. The coexisting components of Coptidis Rhizoma could inhibit the excretion of magnoflorine in rat bile, urine, and feces, which was consistent with the decrease in the elimination rate of magnoflorine in the pharmacokinetics of Coptidis Rhizoma water decoction. It indicated interactions between drugs. This study is expected to provide references for the development of magnoflorine-containing new drugs and rational clinical medication of Coptidis Rhizoma.
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Aporfinas , Medicamentos Herbarios Chinos , Animales , Bilis , Coptis chinensis , Medicamentos Herbarios Chinos/farmacología , Heces , Ratas , AguaRESUMEN
The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 µm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 µg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.
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Verde de Indocianina , Morfinanos , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Agujas , PolietilenglicolesRESUMEN
To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-ß-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.
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Ácidos y Sales Biliares , Trastornos del Inicio y del Mantenimiento del Sueño , Animales , Cromatografía Liquida , Medicamentos Herbarios Chinos , Íleon , Hígado , Ratones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Espectrometría de Masas en TándemRESUMEN
People are assumed to represent themselves in terms of body ownership and agency. Studies using the rubber- or virtual-hand illusion have assessed ownership and agency by means of explicit ownership and agency ratings and implicit measures, like proprioceptive drift in the case of ownership. These measures often show similar effects but also some discrepancies, suggesting that they rely on data sources that overlap, but not completely. To systematically assess commonalities and discrepancies, we adopted an immersed virtual hand illusion (VHI) design, in which three independent factors were manipulated: the synchrony between the movement of real and virtual effector, the type of effector, which was a virtual hand or triangle, and the spatial congruency between the real and virtual effector. Commonalities and discrepancies in the effects of these factors were assessed by crossing explicit and implicit measures for ownership and agency. While standard ratings were used as explicit measures, implicit ownership was assessed by means of proprioceptive drift and implicit agency by means of intentional binding. Results showed similar effect patterns for the two agency measures, which, however, were not correlated, different effect patterns for the two ownership measures, and a strong correlation between the two explicit measures. Taken altogether, our findings suggest that explicit and implicit measures of ownership and agency partly rely on shared informational sources, but seem to differ with respect to other sources that are integrated or with respect to the processed dimension (shape vs. time). The findings also suggest that some findings obtained with RHI designs might reflect more the unnatural situation that that design puts individuals into rather than generalizable mechanisms of computing perceived ownership and agency.
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Ilusiones , Percepción del Tacto , Mano , Humanos , Propiedad , PropiocepciónRESUMEN
HDACs as important targets for cancer therapy have attracted extensive attentions. In this work, a series of sixteen hydroxamic acid based HDAC inhibitors were designed and synthesized with 4,5,6,7-tetrahydrobenzothiazole as the structural core. Majority of them exhibited potent inhibitory activities against HDACs and one leading compound 6h was dug out. 6h was proven to be a pan-HDAC inhibitor and displayed high cytotoxicity against seven human cancer cell lines with IC50 values in low micromolar range. 6h could arrest cell cycle in G2/M phase and induce apoptosis in A549 cells. Moreover, compound 6h exhibited remarkable anti-migration and anti-angiogenesis activities. At the same time, 6h was able to elevate the expression of acetylated α-tubulin and acetylated histone H3 in a dose-dependent manner. Docking simulation revealed that 6h fitted well into the active sites of HDAC2 and 6. Finally, compound 6h also exerted potent antitumor effects in an A549 zebrafish xenograft model. Our study demonstrated that compound 6h was a promising candidate for further preclinical studies.