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The design of mutifunctional protein films for large-area spatially ordered arrays of functional components holds great promise in the field of biomedical applications. Herein, interfacial electrostatic self-assembly was employed to construct a large-scale protein thin film by inducing electrostatic interactions between three bovine serum albumin (BSA)-coated nanoclusters and cetyltrimethylammonium bromide (CTAB), leading to their spontaneous organization and uniform distribution at the oil-water interface. This protein film demonstrated excellent multienzyme functions, high antibacterial activity, and pH-responsive drug release capability. Therefore, it can accelerate the wound closure process through a synergistic effect that includes reducing local blood glucose levels, regulating cellular oxidative stress, eradicating bacteria, and promoting cell proliferation.
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The perovskite crystal structure represents a semiconductor material poised for widespread application, underpinned by attributes encompassing heightened efficiency, cost-effectiveness and remarkable flexibility. Notably, strontium titanate (SrTiO3)-type perovskite, a prototypical ferroelectric dielectric material, has emerged as a pre-eminent matrix material for enhancing the energy storage capacity of perovskite. Typically, the strategy involves augmenting its dielectric constant through doping to enhance energy storage density. However, SrTiO3 doping data are plagued by significant dispersion, and the small sample size poses a formidable research hurdle, hindering the investigation of dielectric property and energy storage density enhancements. This study endeavours to address this challenge, our foundation lies in the compilation of 200 experimental records related to SrTiO3-type perovskite doping, constituting a small dataset. Subsequently, an interactive framework harnesses deep neural network models and a one-dimensional convolutional neural network model to predict and scrutinize the dataset. Distinctively, the mole percentage of doping elements exclusively serves as input features, yielding significantly enhanced accuracy in dielectric performance prediction. Lastly, rigorous comparisons with traditional machine learning models, specifically gradient boosting regression, validate the superiority and reliability of deep learning models. This research advances a novel, effective methodology and offers a valuable reference for designing and optimizing perovskite energy storage materials.
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Photosynthesis is a complex multi-step process in which light collection is the initial step of photosynthesis and plays an important role in the efficiency of solar energy utilization. In order to improve the utilization of sunlight, researchers have developed a variety of artificial light-harvesting system to simulate photosynthesis in nature. Here, we report a supramolecular self-assembly artificial light-harvesting system in aqueous solution. We modified ß-CD with the donor molecule naphthalimide and adamantane with the tetraphenylethylene molecule which has aggregation-induced emission effects (AIE). By using fluorescent molecules with AIE, the self-quenching effect caused by aggregation in aqueous solution can be effectively avoided. Due to the host-guest interaction of ß-CD and adamantane, nanoparticles with stable structure and uniform size can be spontaneously assembled in water. Because of the close distance and strong spectral overlap between naphthalimide and tetraphenylethylene, Förster resonance energy transfer (FRET) was realized, and artificial light-harvesting system was successfully constructed in aqueous solution. The light-harvesting system has a high energy transfer efficiency (ΦET). Therefore, this study provides a new strategy for constructing artificial light-harvesting system.
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Multi-band terahertz (THz) absorbers have recently gained attention due to their favorable application prospects in communication, imaging, detection, and other fields. However, many multi-band THz absorbers are tuned by a single method, which limits their tuning effect. To address this issue, we propose a multi-band THz absorber that can be co-modulated by thermal and electrical methods. Our proposed absorber uses vanadium dioxide (VO2) to achieve this co-modulation. When VO2 is insulating, the frequency of the absorbing peaks originating from the lateral Fabry-Pérot resonance mode can be changed by adjusting the VO2 width. When VO2 is a conductor, the quality factor of the absorbing peak based on the inductor-capacitor resonance mode can be tuned by adjusting the width of VO2. By varying the top dielectric layer thickness, the frequency of the absorbing peaks can be tuned over a wide range. For devices with two or three layers of graphene nanoribbons-dielectric stacks, a modulation effect similar to that of varying dielectric layer thickness in a single-layer graphene device can be achieved simply by applying a 1 eV Fermi energy to graphene nanoribbons in different layers. By combining thermal and electrical modulation, the two or three-layer stacked device can be dynamically switched between four or six absorbing states, and a wider range of dynamic peak frequency modulation can be realized. Furthermore, the performance of the absorber does not deteriorate significantly at an incident angle of up to 70°. Our proposed thermal-electrical switchable wide-angle multi-band THz absorber provides a reference for the design, fabrication, and application of high-performance THz absorbers in different fields.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.
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Terapia por Acupuntura , Enfermedad Pulmonar Obstructiva Crónica , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Aberrant keratinocytes differentiation has been demonstrated to be associated with a number of skin diseases. The roles of lncRNAs in keratinocytes differentiation remain to be largely unknown. OBJECTIVE: Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation. METHODS: Expression of lnc-DC in the skin was queried in AnnoLnc and verified by FISH. The lncRNA expression profiles during keratinocytes differentiation were reanalyzed and verified by qPCR and FISH. Gene knock-down and over-expression were used to explore the role of lnc-DC in keratinocytes differentiation. The downstream target of lnc-DC was screened by whole transcriptome sequencing. CUT&RUN assay and siRNAs transfection was used to reveal the regulatory effect of GRHL3 on lnc-DC. The mechanism of lnc-DC regulating ZNF750 was revealed by RIP assay and RNA stability assay. RESULTS: Lnc-DC was biasedly expressed in skin and up-regulated during epidermal keratinocytes differentiation. Knockdown lnc-DC repressed epidermal keratinocytes differentiation while over-express lnc-DC showed the opposite effect. GRHL3, a well-known transcription factor regulating keratinocytes differentiation, could bind to the promoter of lnc-DC and regulate its expression. By whole transcriptome sequencing, we identified that ZNF750 was a downstream target of lnc-DC during keratinocytes differentiation. Mechanistically, lnc-DC interacted with RNA binding protein IGF2BP2 to stabilize ZNF750 mRNA and up- regulated its downstream targets TINCR and KLF4. CONCLUSION: Our study revealed the novel role of GRHL3/lnc-DC/ZNF750 axis in regulating epidermal keratinocytes differentiation, which may provide new therapeutic targets of aberrant keratinocytes differentiation related skin diseases.
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ARN Largo no Codificante , Enfermedades de la Piel , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción/metabolismo , Queratinocitos/metabolismo , Piel/metabolismo , Enfermedades de la Piel/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 (R)-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of (R)-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using (R)-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35-40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5-20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM (R)-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product (R)-2-(1-aminoethyl)-4-fluorophenol with high (R)-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production.
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Antineoplásicos , Fenoles , Transaminasas , Dimetilsulfóxido , Escherichia coli , Cetonas , Antineoplásicos/farmacología , Catálisis , EtanolRESUMEN
Glucosylglycerol (GG) is a natural compatible solute that can be synthesized by many cyanobacteria and a few heterotrophic bacteria under high salinity conditions. In cyanobacteria, GG is synthesized by GG-phosphate synthase and GG-phosphate phosphatase, and a hydrolase GGHA catalyzes its degradation. In heterotrophic bacteria (such as some Marinobacter species), a fused form of GG-phosphate phosphatase and GG-phosphate synthase is present, but the cyanobacteria-like degradation pathway is not available. Instead, a phosphorylase GGP, of which the coding gene is located adjacent to the gene that encodes the GG-synthesizing enzyme, is supposed to perform the GG degradation function. In the present study, a GGP homolog from the salt-tolerant M. salinexigens ZYF650T was characterized. The recombinant GGP catalyzed GG decomposition via a two-step process of phosphorolysis and hydrolysis in vitro and exhibited high substrate specificity toward GG. The activity of GGP was enhanced by inorganic salts at low concentrations but significantly inhibited by increasing salt concentrations. While the investigation on the physiological role of GGP in M. salinexigens ZYF650T was limited due to the failed induction of GG production, the heterologous expression of ggp in the living cells of the GG-producing cyanobacterium Synechocystis sp. PCC 6803 significantly reduced the salt-induced GG accumulation. Together, these data suggested that GGP may represent a novel pathway of microbial GG catabolism. KEY POINTS: ⢠GGP catalyzes GG degradation by a process of phosphorolysis and hydrolysis ⢠GGP-catalyzed GG degradation is different from GGHA-based GG degradation ⢠GGP represents a potential novel pathway of microbial GG catabolism.
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Glucósidos , Fosforilasas , Synechocystis , Fosforilasas/química , Monoéster Fosfórico Hidrolasas/genética , FosfatosRESUMEN
The vegetation ecosystem in the southern hilly region of China (SHRC) plays a crucial role in the country's carbon reservoir. Clarifying the dynamics of net primary productivity (NPP) in this area and its response to climate factors in the context of climate change is important for national forest ecology, management, and carbon neutrality efforts. This study, based on remote sensing and meteorological data spanning the period 2001 to 2021, aims to unveil the spatiotemporal patterns of vegetation productivity and climate factors in the southern hilly region, explore interannual variation characteristics of vegetation productivity with altitude, and investigate the response characteristics of NPP to various climate factors. The results indicate that from 2001 to 2021, the annual average NPP in the southern hilly region had a significant increasing trend of 2.13 ± 0.78 g m-2 a-1. The trend of NPP varies significantly with altitude. Despite a general substantial upward trend in vegetation NPP, regions at lower elevations exhibit a faster rate of increase, suggesting a diminishing difference in the NPP of different elevation ranges. The overall rise in average temperature has positive implications for the southern hilly region, while the impact of precipitation on vegetation NPP demonstrates noticeable spatial heterogeneity. Regions in which vegetation NPP is significantly negatively correlated with precipitation are mainly concentrated in the southern areas of Guangdong, Fujian, and Jiangxi provinces. In contrast, other regions further away from the southeastern coast tend to exhibit a positive correlation. Over the past two decades, there has been an asymmetry in the diurnal temperature variation in the SHRC, with the nighttime warming rate being 1.8 times that of the daytime warming rate. The positive impact of daytime warming on NPP of vegetation is more pronounced than the impact of nighttime temperature changes. Understanding the spatiotemporal patterns of NPP in the SHRC and the characteristics of its response to climate factors contributes to enhancing our ability to protect and manage vegetation resources amidst the challenges of global climate change.
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The development of cell-like nanoreactors with the ability to initiate biocatalytic cascades under special conditions holds tremendous potential for therapeutic applications. Herein, conformationally gated nanoreactors that respond to the acidic microenvironment of infected diabetic wounds were developed by cucur[8]bituril (CB[8])-based supramolecular assembly. The bioinspired nanoreactors exhibit not only self-regulated permeability and selectivity to control internal enzyme activities by substance exchange but also distinct binding specificities toward Gram-positive and Gram-negative bacteria via noncovalent modification with different ligands. The encapsulation of glucose oxidase (GOx), Fe3O4 nanozyme, and l-arginine (l-Arg) into the nanocarriers enables intelligent activation of multienzyme cascade reactions upon glucose (Glu) uptake to produce gluconic acid (GA) and hydrogen peroxide (H2O2), which is further converted into highly toxic hydroxyl radicals (·OH) for selective antibacterial activity. Moreover, acidic H2O2 promotes the oxidization of l-Arg, leading to the release of nitric oxide (NO). Consequently, this nanoreactor provides a multifunctional and synergistic platform for diabetic chronic wound healing by combining enzyme dynamic therapy with NO gas therapy to combat bacterial infections and inflammation under high blood Glu levels.
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Antibacterianos , Diabetes Mellitus , Humanos , Antibacterianos/farmacología , Peróxido de Hidrógeno , Bacterias Gramnegativas , Bacterias Grampositivas , Arginina , Glucosa Oxidasa , Óxido Nítrico , Cicatrización de Heridas , NanotecnologíaRESUMEN
MYB family genes have many functions and are widely involved in plant abiotic-stress responses. Erianthus fulvus is an important donor material for stress-resistance genes in sugarcane breeding. However, the MYB family genes in E. fulvus have not been systematically investigated. In this study, 133 EfMYB genes, including 48 Ef1R-MYB, 84 EfR2R3-MYB and 1 Ef3R-MYB genes, were identified in the E. fulvus genome. Among them, the EfR2R3-MYB genes were classified into 20 subgroups. In addition, these EfMYB genes were unevenly distributed across 10 chromosomes. A total of 4 pairs of tandemly duplicated EfMYB genes and 21 pairs of segmentally duplicated EfMYB genes were identified in the E. fulvus genome. Protein-interaction analysis predicted that 24 EfMYB proteins had potential interactions with 14 other family proteins. The EfMYB promoter mainly contains cis-acting elements related to the hormone response, stress response, and light response. Expression analysis showed that EfMYB39, EfMYB84, and EfMYB124 could be significantly induced using low-temperature stress. EfMYB30, EfMYB70, EfMYB81, and EfMYB101 responded positively to drought stress. ABA treatment significantly induced EfMYB1, EfMYB30, EfMYB39, EfMYB84, and EfMYB130. All nine genes were induced using MeJA treatment. These results provide comprehensive information on EfMYB genes and can serve as a reference for further studies of gene function.
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Familia de Multigenes , Saccharum , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Filogenia , Saccharum/genética , Saccharum/metabolismo , FitomejoramientoRESUMEN
BACKGROUND: The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1 (PD-L1), which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases. In MSCs, interferon-gamma (IFN-γ) is a key inducer of PD-L1 expression, which is synergistically enhanced by tumor necrosis factor-alpha (TNF-α); however, the underlying mechanism is unclear. AIM: To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis. METHODS: We assessed PD-L1 expression in human umbilical-cord-derived MSCs (hUC-MSCs) induced by IFN-γ and TNF-α, alone or in combination. Additionally, we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γ alone or in combination with TNF-α induces PD-L1 expression. Moreover, we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters. Finally, we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γ and TNF-α in both an in vitro mixed lymphocyte culture assay, and in vivo in mice with dextran sulfate sodium-induced acute colitis. RESULTS: Our results suggest that IFN-γ induction alone upregulates PD-L1 expression in hUC-MSCs while TNF-α alone does not, and that the co-induction of IFN-γ and TNF-α promotes higher expression of PD-L1. IFN-γ induces hUC-MSCs to express PD-L1, in which IFN-γ activates the JAK/STAT1 signaling pathway, up-regulates the expression of the interferon regulatory factor 1 (IRF1) transcription factor, promotes the binding of IRF1 and the PD-L1 gene promoter, and finally promotes PD-L1 mRNA. Although TNF-α alone did not induce PD-L1 expression in hUC-MSCs, the addition of TNF-α significantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation. TNF-α up-regulated IFN-γ receptor expression through activation of the nuclear factor kappa-B signaling pathway, which significantly enhanced IFN-γ signaling. Finally, co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation, and significantly ameliorate weight loss, mucosal damage, inflammatory cell infiltration, and up-regulation of inflammatory factors in colitis mice. CONCLUSION: Overall, our results suggest that IFN-γ and TNF-α enhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.
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BACKGROUND: Port wine stains slowly grow thicker over time, nodules appear on the surface, and the color slowly deepens from pink to purple. Even after laser treatment, some port wine stains will recur and slowly grow, and the erythema appears again. The purpose of this study was to investigate the effectiveness of bleomycin in combination with triamcinolone acetonide in the treatment of inhibiting the proliferation and recurrence of port wine stains. RESULTS: Histopathological change: Before treatment, dense capillaries were distributed within the lesion, and blood fills the lumen. Lack of normal skin structure: After bleomycin and triamcinolone acetonide injection, the number of capillaries was significantly reduced, and fibrosis occurred in tissues. Changes in facial morphology: After treatment, the port wine stains became thinner, the asymmetry of the face was effectively improved, and the appearance have been significantly improved. After 5 years of follow-up, there were no recurrent cases. CONCLUSION: Bleomycin and triamcinolone acetonide injection can effectively inhibit the proliferation of port wine stains and prevent port wine stains from recurring after treatment.
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ω-transaminases are able to catalyze the reversible transfer of amino groups between diverse amino compounds (such as amino acids, alkyl amines, aromatic amines) and carbonyl compounds (such as aldehydes, ketones, ketoacids). ω-transaminases exhibit great application prospects in the field of chiral amine biosynthesis because of their desirable properties, such as wide range of substrates, high stereoselectivity, and mild catalytic conditions. It is therefore important for China to develop efficient, specific, and environment-friendly chiral amine production technologies with independent intellectual property rights, which is of great significance for the development of pharmaceutical, pesticide, and material industries. This review systematically summarizes the Chinese patents regarding ω-transaminase filed by Chinese institutions in the recent decade. The development of ω-transaminase resource, enzymatic property improvement by protein engineering, application in chiral amine synthesis, and development of production technologies are elaborated. This review will shed light on further basic and application studies of ω-transaminase.
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Aminoácidos , Transaminasas , Transaminasas/genética , China , Aldehídos , AminasRESUMEN
Purpose: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. Methods: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. Results: We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Conclusion: Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.
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Adenocarcinoma , Hipotiroidismo , Neoplasias de la Tiroides , Humanos , Tiroxina/uso terapéutico , Radioisótopos de Yodo , Neoplasias de la Tiroides/cirugía , Lipoproteínas LDLRESUMEN
In nature, enantiomers are pairs of chiral compounds, and have semblable chemical and physical properties but mostly show opposite biological effects when they enter an organism. Therefore, chiral recognition has a crucial research value in the fields of medicine, food, biochemistry, etc. Cyclodextrins (CDs) are produced by cyclodextrin glucosyltransferase in some species of bacillus on starch and include three main members α-, ß-, and γ-CD with six, seven and eight units of glucose, respectively. With a hydrophilic external cavity and a hydrophobic internal cavity, ß-CD can also combine with a variety of materials (e.g., graphene, nanoparticles, COFs, and OFETs) to enhance the chiral recognition of guest molecules in a chiral sensor. This review presents the progress of ß-CD modification with different materials for chiral recognition and describes in detail how different materials assist ß-CD in chiral recognition and improve the effect of ß-CD chiral discrimination.
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A cobalt(III)-catalyzed directed C-7 alkynylation of indolines with easily accessible bromoalkynes has been developed. The reaction has a broad substrate scope with excellent yields and represents a powerful route to the synthesis of 7-alkynyl-substituted indolines. In addition, the reaction can be extended to the coupling of N-aryl 7-azaindoles, highlighting the synthetic practicability of the strategy.
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Precise protein assemblies not only constitute a series of living machineries but also provide an advanced class of biomaterials. Previously, we developed the inducing ligand strategy to generate various fixed protein assemblies, without the formation of noncovalent interactions between proteins. Here, we demonstrated that controlling the symmetry and number of supramolecular interactions introduced on protein surfaces could direct the formation of unspecific interactions between proteins and induce various nanoscale assemblies, including coiling nanowires, nanotubes, and nanosheets, without manipulation of the protein's native surfaces. More importantly, these nanoscale assemblies could spontaneously evolve into more ordered architectures, crystals. We further showed that the transformation from the introduced supramolecular interactions to the interactions formed between proteins was crucial for pathway selection and outcomes of evolution. These findings reveal a transformation mechanism of protein self-assembly that has not been exploited before and may provide an approach to generate complex and transformable biomacromolecular self-assemblies.
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Nanotubos , Nanotubos/química , Proteínas de la MembranaRESUMEN
BACKGROUND: Keloids and hypertrophic scars frustrate patients by the deformity of appearance and organ dysfunction. Many modalities had been tried in clinic practice, but the results are unsatisfied. OBJECTIVE: We retrospectively analysed the combined application of bleomycin and triamcinolone for the treatment of keloids and hypertrophic scars. METHODS: The combination of bleomycin and triamcin acetonide was applied to the treatment of keloids and hypertrophic scars, 86 cases accepted the treatment. Follow-up 2-5 years after treatment. RESULTS: (1) The pain of scars and itching symptoms have basically subsided through treatment. (2) After drug injection treatment, the keloid began to shrink, some of the keloids disappeared. (3) Small keloids did not recur after treatment. Large keloids had local recurrence after treatment. When further treatment was given, the recurrence disappeared. CONCLUSION: The combined application of bleomycin and triamcin acetonide can effectively cure keloids and hypertrophic scars.
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Cicatriz Hipertrófica , Queloide , Humanos , Queloide/tratamiento farmacológico , Queloide/patología , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/patología , Bleomicina/uso terapéutico , Triamcinolona/uso terapéutico , Estudios Retrospectivos , Inyecciones Intralesiones , Resultado del TratamientoRESUMEN
Inspired by nature, it is of significant importance to design and construct biomimetic signaling systems to mimic natural signal transduction. Herein, we report an azobenzene/α-cyclodextrin (α-CD)-based signal transduction system with three functional modules: a light-responsive headgroup, lipid-anchored group, pro-catalyst tailgroup. The transducer can be inserted into the vesicular membrane to trigger the transmembrane translocation of molecules under the activation of light, forming a ribonuclease-like effector site and leading to the transphosphorylation of the RNA model substrate inside the vesicles. Moreover, the transphosphorylation process can be reversibly turned 'ON/OFF' over multiple cycles by the activation and deactivation of the pro-catalyst. This artificial photo-controlled signal transduction successfully constructs a signal responsive catalysis system across the membrane to utilize light to reversibly control the internal transphosphorylation process of an RNA model substrate, which might provide a new strategy for future design to utilize exogenous signals for implementing endogenous enzyme manipulation and gene regulation.