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The formation process of biofouling is actually a 4D process with both spatial and temporal dimensions. However, most traditional antifouling coatings, including slippery liquid-infused porous surface (SLIPS), are limited to performing antifouling process in the 2D coating plane. Herein, inspired by the defensive behavior of sea anemones' wielding toxic tentacles, a "4D SLIPS" (FSLIPS) is constructed with biomimetic cilia via a magnetic field self-assembly method for antifouling. The bionic cilia move in 3D space driven by an external magnetic field, thereby preventing the attachment of microorganisms. The FSLIPS releases the gaseous antifoulant (nitric oxide) at 1D time in response to light, thereby achieving a controllable biocide effect on microorganisms. The FSLIPS regulates the movement of cilia via the external magnetic field, and controls the release of NO overtime via the light response, so as to adjust the antifouling modes on demand during the day or night. The light/magnetic response mechanism endow the FSLIPS with the ability to adjust the antifouling effect in the 4D dimension of 1D time and 3D space, effectively realizing the intelligence, multi-dimensionality and precision of the antifouling process.
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B/T mixed phenotype acute leukemia (MPAL), which represents only 2-3% of all MPAL cases, is classified as a high-risk leukemia subtype. Adults diagnosed with B/T MPAL have a notably low 3-year survival rate, estimated at 20-40%. The rarity and undercharacterization of B/T MPAL present substantial challenges in identifying an optimal treatment protocol. This report aims to shed light on this issue by presenting a case in which a patient with a complex karyotype was treated using a combination of venetoclax, azacitidine, and blinatumomab. This novel, chemo-free regimen resulted in the patient achieving both hematologic and molecular complete remission, with no severe organ or hematological toxicity observed. Notably, the patient continued to maintain molecular remission for 1 year following the transplantation. Based on these findings, the combination of venetoclax, azacitidine, and blinatumomab could be considered a potential therapeutic approach for B/T MPAL patients, meriting further investigation.
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Anticorpos Biespecíficos , Azacitidina , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia , Sulfonamidas , Adulto , Humanos , Azacitidina/uso terapêutico , Leucemia/terapia , Doença AgudaRESUMO
This study aimed to evaluate the efficacy and safety of chidamide (Chi) combined with a modified Busulfan-Cyclophosphamide (mBuCy) conditioning regimen for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only in the same period. The leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse-related mortality (NRM) were evaluated. Patients in the Chi group were associated with lower 2-year CIR (19.0 vs. 41.4%, P = 0.030), better 2-year LFS (76.1 vs. 48.1%, P = 0.014), and had no significant difference in 2-year OS (80.5 vs. 66.4%, P = 0.088). Patients with minimal residual disease (MRD) positive before HSCT in the Chi group exhibited an advantage in 2-year LFS and a trend towards better 2-year OS (75.0 vs. 10.2%, P = 0.048; 75.0 vs. 11.4%, P = 0.060, respectively). Multivariable analysis showed that the chidamide intensified regimen was independently associated with better LFS (HR 0.23; 95%CI, 0.08-0.63; P = 0.004), and showed no significant impact with OS for all patients (HR 0.34, 95%CI, 0.11-1.07; P = 0.064). The cumulative incidence rates of grade II-IV aGVHD were similar (36.4 vs. 38.6%, P = 0.858). 20 patients in Chi group evinced an elevation in γ-glutamyltransferase, as compared to the mBuCy group (90.9 vs. 65.9%, P = 0.029). No transplantation-related mortality was documented within the first 100 days after transplantation. The results demonstrate that the chidamide intensified regimen may be an effective and acceptable safety option for T-ALL/LBL undergoing allo-HSCT, and further validation is needed.
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Condicionamento Pré-Transplante , Humanos , Masculino , Feminino , Condicionamento Pré-Transplante/métodos , Adulto , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Adolescente , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Taxa de Sobrevida , Transplante Homólogo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/mortalidade , Intervalo Livre de Doença , Estudos Retrospectivos , AloenxertosRESUMO
Otoferlin (OTOF) gene mutations represent the primary cause of hearing impairment and deafness in auditory neuropathy. The c.2485C>T (p. Q829X) mutation variant is responsible for approximately 3% of recessive prelingual deafness cases within the Spanish population. Previous studies have used two recombinant AAV vectors to overexpress OTOF, albeit with limited efficacy. In this study, we introduce an enhanced mini-dCas13X RNA base editor (emxABE) delivered via an AAV9 variant, achieving nearly 100% transfection efficiency in inner hair cells. This approach is aimed at treating OTOFQ829X, resulting in an approximately 80% adenosine-to-inosine conversion efficiency in humanized OtofQ829X/Q829X mice. Following a single scala media injection of emxABE targeting OTOFQ829X (emxABE-T) administered during the postnatal day 0-3 period in OtofQ829X/Q829X mice, we observed OTOF expression restoration in nearly 100% of inner hair cells. Moreover, auditory function was significantly improved, reaching similar levels as in wild-type mice. This enhancement persisted for at least 7 months. We also investigated P5-P7 and P30 OtofQ829X/Q829X mice, achieving auditory function restoration through round window injection of emxABE-T. These findings not only highlight an effective therapeutic strategy for potentially addressing OTOFQ829X-induced hearing loss but also underscore emxABE as a versatile toolkit for treating other monogenic diseases characterized by premature termination codons.
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Surdez , Perda Auditiva Central , Perda Auditiva , Animais , Camundongos , Edição de Genes , Perda Auditiva/genética , Perda Auditiva/terapia , MutaçãoRESUMO
Microplastic (MP) pollution has become a pressing concern in global freshwater ecosystems because rivers serve as essential channels for the transport of terrestrial debris to the ocean. The current researches mostly focus on the large catchments, but the impact on the small catchments remains underexplored. In this study, we employed Strahler's stream order classification to delineate the catchment structure of the Beijiang River in South China. The distribution pattern of MP contamination and the factors influencing the distribution pattern, were assessed across the streams at different orders. We found that the Beijiang River was moderately polluted compare to other rivers in China, with an average MP abundance of 2.15 ± 1.65 items/L. MP abundance ranged from 3.17 to 1.45 items/L in the streams at different orders, and significantly decreased with increasing stream order (R2 = 0.93). This highlights the key role of small rivers as the channels for the transport of MPs from watersheds to main streams. The high abundance of PP and PE fibers, the high correlation between the stream order and the resin proportion (R2 = 0.89), and the significant correlation between MP abundance and proximity to urban centers (P = 0.02), indicated that MP pollution across the streams at different orders was predominantly influenced by anthropogenic activities, rather than natural environmental factors. By integrating MP data with hydrographic information, the annual MP loads for the streams at Orders 1 to Order 5 were estimated to be 4.63, 39.38, 204.63, 503.06, and 1137.88 tons/yr, respectively. Additionally, an ecological risk assessment indicates that MP pollution led to a low risk in the Beijiang River. Our findings deepen the understanding of MP pollution within freshwater river networks, and emphasize the crucial role of tributary systems in transporting MPs to main river channels.
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Monitoramento Ambiental , Microplásticos , Rios , Rios/química , Microplásticos/análise , China , Água Doce/química , Poluentes Químicos da Água/análise , EcossistemaRESUMO
In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310â mAh g-1 under -30 °C, respectively, showing long-term cycling stability and great rate capability at low temperature.
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Accurate communication between fibroblasts and keratinocytes is crucial for diabetic wound healing. Extracellular vesicles are being explored as essential mediators of intercellular communication in the skin. However, the mechanisms underlying wound healing mediated by fibroblast-derived extracellular vesicles (Fib-EVs) remain unclear. The present study evaluated the role of long noncoding RNA upregulated in diabetic skin (lnc-URIDS) packed in Fib-EVs in the wound healing of streptozotocin-induced diabetes and the potential mechanisms of the effects. We demonstrated that high glucose induced the enrichment of lnc-URIDS in Fib-EVs, facilitated the transfer of lnc-URIDS to primary rat epidermal keratinocytes, and increased the expression of matrix metalloproteinase-9. Mechanistically, the binding of lnc-URIDS to YTH domain family protein-2 enhanced the degradation of YTH domain family protein-2 in the lysosomes, which increased the translational activity of the messenger RNA of matrix metalloproteinase-9 and ultimately induced the degradation of collagen for wound healing. The results provided an insight into the crosstalk and cooperation between fibroblasts and keratinocytes in collagen homeostasis in diabetic wounds and clarified the mechanism by which lnc-URIDS degrades collagen for diabetic wound healing.
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Diabetes Mellitus Experimental , Vesículas Extracelulares , RNA Longo não Codificante , Animais , Ratos , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Vesículas Extracelulares/metabolismo , Fibroblastos/metabolismo , Queratinócitos/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Pele/metabolismo , Cicatrização/genéticaRESUMO
Conventional wind speed sensors face difficulties in measuring wind speeds at multiple points, and related research on predicting rotor effective wind speed (REWS) is lacking. The utilization of a lidar device allows accurate REWS prediction, enabling advanced control technologies for wind turbines. With the lidar measurements, a data-driven prediction framework based on empirical mode decomposition (EMD) and gated recurrent unit (GRU) is proposed to predict the REWS. Thereby, the time series of lidar measurements are separated by the EMD, and the intrinsic mode functions (IMF) are obtained. The IMF sequences are categorized into high-, medium-, and low-frequency and residual groups, pass through the delay processing, and are respectively used to train four GRU networks. On this basis, the outputs of the four GRU networks are lumped via weighting factors that are optimized by an equilibrium optimizer (EO), obtaining the predicted REWS. Taking advantages of the measurement information and mechanism modeling knowledge, three EMD-GRU prediction schemes with different input combinations are presented. Finally, the proposed prediction schemes are verified and compared by detailed simulations on the BLADED model with four-beam lidar. The experimental results indicate that compared to the mechanism model, the mean absolute error corresponding to the EMD-GRU model is reduced by 49.18%, 53.43%, 52.10%, 65.95%, 48.18%, and 60.33% under six datasets, respectively. The proposed method could provide accurate REWS prediction in advanced prediction control for wind turbines.
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The experiment aimed to compare the effects of citric acid residue (CAR) to that of three commonly used short-chain fatty acids on the fermentation quality, aerobic stability and structural carbohydrate degradation of lucerne ensiled with lactic acid bacteria (LAB) inoculants. Fresh lucerne was ensiled with distilled water (control), LAB inoculant (L), CAR + LAB inoculant (CL), formic acid + LAB inoculant (FL), acetic acid + LAB inoculant (AL) and propanoic acid + LAB inoculant (PL) for 50 days. Chemical composition and microbial populations were determined after ensiling. The residual silages ensiled for 50 days were evaluated for aerobic stability. Compared with control, CL, FL, AL and PL treatments significantly (p < 0.05) decreased pH, ammonia nitrogen (NH3 -N) and butyric acid contents and increased lactic acid, acetic acid and propionic acid contents. Among them, CL silages had the lowest pH, dry matter and water-soluble carbohydrate (WSC) content, whereas the population of LAB and the lactic acid contents were highest. Besides, CL outperformed in enhancing fibre degradation, CL silages significantly decreased (p < 0.05) neutral detergent fibre, acid detergent fibre, hemicellulose and cellulose contents compared with control and had the highest Flieg's point. All treated-silages improved the aerobic stability compared with control, of which L improved 32 h, whereas CL, FL, AL and PL improved 46, 20, 46, >64 h, respectively. Applying a combination of CAR and LAB inoculant improved the fermentation quality and structural carbohydrate degradation of lucerne silage and had a similar effect on aerobic stability compared with other three short-chain fatty acids. The CAR had a comparable effect on enhancing the fermentation quality compared with three short-chain fatty acids. Thus, the combination of CAR and LAB inoculant might be used as an ideal additive for lucerne silage making with low WSC and high moisture content.
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Inoculantes Agrícolas , Medicago sativa , Ácido Acético , Aerobiose , Ácido Cítrico , Fermentação , Ácido Láctico , Lactobacillus , Silagem/análiseRESUMO
Increased matrix metalloproteinase 9 (MMP9) expression is involved in delayed wound healing in diabetic foot ulcers. We created skin wounds in normal SD rats and STZ-induced diabetic SD rats, then we found protein levels of activator protein-1 (AP1), a crucial transcription factor to increase MMP9 transcription, as well as MMP9 was up-regulated in epithelium of diabetic skin tissues. Then, we evaluated the mRNA and protein stability of AP1 subunits C-FOS/C-Jun in HaCaT cells after high glucose treatment. Results showed that high glucose could increase protein stability of C-FOS and C-Jun. Additionally, high glucose also activated extracellular signaling-related kinase 1/2 (ERK1/2). ERK1/2 inhibitor could rescue phosphorylation of C-FOS and C-Jun, increased protein stability of C-Jun, and increased MMP9 expressions. Thus, our study demonstrated that high glucose could activate ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic skin and HaCaT cells.
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Pé Diabético/tratamento farmacológico , Glucose/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Vascular metabolic dysfunction presents in various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. Due to the high prevalence of these diseases, it is important to explore treatment strategies to protect vascular function. Resveratrol (RSV), a natural polyphenolic phytochemical, is regarded as an agent to regulate metabolic pathways. Many studies have proven that RSV has beneficial effects on improving metabolism in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which provide new directions to treat vascular metabolic diseases. Herein, we overviewed that RSV could regulate cell metabolism activity by inhibiting glucose uptake, suppressing glycolysis, preventing cells from fatty acid-related damages, reducing lipogenesis, increasing fatty acid oxidation, enhancing lipolysis, elevating uptake and synthesis of glutamine, and increasing NO release. Furthermore, in clinical trials, although the results from different studies remain controversial, we proposed that RSV had better therapeutic effects at high concentrations and for patients with metabolic disorders.
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Doenças Metabólicas , Estilbenos , Doenças Vasculares , Humanos , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Células Endoteliais/metabolismo , Doenças Metabólicas/tratamento farmacológico , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo , Estilbenos/farmacologiaRESUMO
It has long been a challenge to fabricate angstrom-sized functional pores for mimicking the function of biological channels to afford selective transmembrane transport. In this study, we describe a facile strategy to incorporate ionic elements into angstrom-sized channels using de novo encapsulation of charged dye molecules during the interface polymerization of a three-dimensional covalent organic framework (3D COF). We demonstrate that this approach is tailorable as it enables control over both the type and content of the guest and thus allows manipulation of the membrane function. The resulting membranes exhibit excellent permselectivity and low membrane resistance, thereby indicating the potential for harvesting salinity gradient (blue) energy. As a proof-of-concept study, the reverse electrodialysis device coupled with positive and negative dye encapsulated COF membranes afforded a power density of up to 51.4 W m-2 by mixing the simulated seawater and river water, which far exceeds the commercialization benchmark (5 W m-2). We envision that this strategy will pave the way for constructing new multifunctional biomimetic systems.
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Obesity has become an epidemic concern in modern society. The chronic obesity is associated with metabolic disorders, such as hyperglycemia, hyperlipidemia, fatty liver, and cadiovascular disease, which cause high risk for mortality. The novel potential strategy to overcome obesity is to "burn out" the extra fat via "browning" of the white adipose tissues. The phytochemical resveratrol (Res) has attracted substantial attention due to its powerful amelioratory effects in metabolic diseases. However, how Res regulates the browning of adipose tissues remains largely elusive. Our data show that the NAD+ -dependent deacetylase silent information regulator 1 (Sirt1) mediates Res-induced browning and fat reduction of adipocytes, as well as other Res-improved metabolic phenotypes including hyperglycemina and hyperlipidemia in mice. Interestingly, we found that the major metabolites of Res in vivo (Res-3-O-glucuronide, Res-4'-O-glucuronide, and Res-3-O-sulfate) were much less potent in promoting browning gene expressions and reducing fat content in comparison to Res itself in mouse and human adipocytes in vitro, suggesting the importance and necessarity to enhance the bioavailability of Res in vivo in consideration of therapeutic application. Taken together, our findings clarify the beneficial effects of Res on excess fat utilization via promotion of browning in a Sirt1-dependent manner, suggesting the potential therapeutic application of Res in the treatment of obesity and related metabolic disorders.
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Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Colesterol/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sirtuína 1/metabolismo , Células 3T3-L1 , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Reação em Cadeia da Polimerase em Tempo Real , Sirtuína 1/genéticaRESUMO
Sirtuins are NAD(+)-dependent protein deacetylases that connect metabolism and cellular homeostasis. Here we show that the nuclear Sirtuin SIRT7 targets PAF53, a subunit of RNA polymerase I (Pol I). Acetylation of PAF53 at lysine 373 by CBP and deacetylation by SIRT7 modulate the association of Pol I with DNA, hypoacetylation correlating with increased rDNA occupancy of Pol I and transcription activation. SIRT7 is released from nucleoli in response to different stress conditions, leading to hyperacetylation of PAF53 and decreased Pol I transcription. Nucleolar detention requires binding of SIRT7 to nascent pre-rRNA, linking the spatial distribution of SIRT7 and deacetylation of PAF53 to ongoing transcription. The results identify a nonhistone target of SIRT7 and uncover an RNA-mediated mechanism that adapts nucleolar transcription to stress signaling.
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RNA Polimerase I/genética , Sirtuínas/metabolismo , Fatores de Transcrição/metabolismo , Ativação Transcricional/genética , Acetilação , Proteína de Ligação a CREB/metabolismo , Células HEK293 , Humanos , Lisina/genética , RNA Polimerase I/antagonistas & inibidores , Precursores de RNA/metabolismo , Sirtuínas/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genéticaRESUMO
Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current development drug therapy to promote angiogenesis is limited. Resveratrol (RSV), a polyphenol compound extracted from plants, has various properties such as anti-oxidative, anti-inflammatory and anti-cancer effects. Whether RSV exerts protective effects on CLI remains elusive. In the current study, we demonstrated that oral intake of RSV significantly improved hind limb ischemia in mice, and increased the expression of phosphorylated Forkhead box class-O1 (FoxO1). RSV treatment in human umbilical vein endothelial cells (HUVECs) could increase the phosphorylation of FoxO1 and its cytoplasmic re-localization to promote angiogenesis. Then we manipulated FoxO1 in HUVECs to further verify that the effect of RSV on angiogenesis is in a FoxO1-dependent manner. Furthermore, we performed metabolomics to screen the metabolic pathways altered upon RSV intervention. We found that the pathways of pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism, were highly correlated with the beneficial effects of RSV on the ischemic muscle. This study provides a novel direction for the medical therapy to CLI.
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Isquemia Crônica Crítica de Membro/tratamento farmacológico , Proteína Forkhead Box O1/metabolismo , Neovascularização Patológica/tratamento farmacológico , Resveratrol/farmacologia , Animais , Isquemia Crônica Crítica de Membro/metabolismo , Proteína Forkhead Box O1/genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
Various robust, crystalline, and porous organic frameworks based on in situ-formed imine-linked oligomers were investigated. These oligomers self-assembled through collaborative intermolecular hydrogen bonding interactions via liquid-liquid interfacial reactions. The soluble oligomers were kinetic products with multiple unreacted aldehyde groups that acted as hydrogen bond donors and acceptors and directed the assembly of the resulting oligomers into 3D frameworks. The sequential formation of robust covalent linkages and highly reversible hydrogen bonds enforced long-range symmetry and facilitated the production of large single crystals, with structures that were unambiguously determined by single-crystal X-ray diffraction. The unique hierarchical arrangements increased the steric hindrance of the imine bond, which prevented attacks from water molecules, greatly improving the stability. The multiple binding sites in the frameworks enabled rapid sequestration of micropollutant in water.
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The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract-treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels.
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Metaloproteinase 16 da Matriz/genética , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Feminino , Genótipo , Haplótipos , Humanos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
GNSS information is vulnerable to external interference and causes failure when unmanned aerial vehicles (UAVs) are in a fully autonomous flight in complex environments such as high-rise parks and dense forests. This paper presents a pan-tilt-based visual servoing (PBVS) method for obtaining world coordinate information. The system is equipped with an inertial measurement unit (IMU), an air pressure sensor, a magnetometer, and a pan-tilt-zoom (PTZ) camera. In this paper, we explain the physical model and the application method of the PBVS system, which can be briefly summarized as follows. We track the operation target with a UAV carrying a camera and output the information about the UAV's position and the angle between the PTZ and the anchor point. In this way, we can obtain the current absolute position information of the UAV with its absolute altitude collected by the height sensing unit and absolute geographic coordinate information and altitude information of the tracked target. We set up an actual UAV experimental environment. To meet the calculation requirements, some sensor data will be sent to the cloud through the network. Through the field tests, it can be concluded that the systematic deviation of the overall solution is less than the error of GNSS sensor equipment, and it can provide navigation coordinate information for the UAV in complex environments. Compared with traditional visual navigation systems, our scheme has the advantage of obtaining absolute, continuous, accurate, and efficient navigation information at a short distance (within 15 m from the target). This system can be used in scenarios that require autonomous cruise, such as self-powered inspections of UAVs, patrols in parks, etc.
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SIRT7 is an NAD+-dependent protein deacetylase that regulates cell growth and proliferation. Previous studies have shown that SIRT7 is required for RNA polymerase I (Pol I) transcription and pre-rRNA processing. Here, we took a proteomic approach to identify novel molecular targets and characterize the role of SIRT7 in non-nucleolar processes. We show that SIRT7 interacts with numerous proteins involved in transcriptional regulation and RNA metabolism, the majority of interactions requiring ongoing transcription. In addition to its role in Pol I transcription, we found that SIRT7 also regulates transcription of snoRNAs and mRNAs. Mechanistically, SIRT7 promotes the release of P-TEFb from the inactive 7SK snRNP complex and deacetylates CDK9, a subunit of the elongation factor P-TEFb, which activates transcription by phosphorylating serine 2 within the C-terminal domain (CTD) of Pol II. SIRT7 counteracts GCN5-directed acetylation of lysine 48 within the catalytic domain of CDK9, deacetylation promoting CTD phosphorylation and transcription elongation.
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Quinase 9 Dependente de Ciclina/metabolismo , RNA Polimerase II/metabolismo , Sirtuínas/metabolismo , Ativação Transcricional , Linhagem Celular , Humanos , Fator B de Elongação Transcricional Positiva/metabolismo , RNA/metabolismo , RNA Nucleolar Pequeno/biossíntese , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Sirtuínas/químicaRESUMO
Resveratrol is identified as polyphenolic compound with anti-inflammatory, antioxidant, anti-insulin resistance characteristics. Moreover, resveratrol exerts pro-apoptotic effects in varieties of cancer cell lines. However, effects and mechanisms of resveratrol on the regulation of adipocytes apoptosis remain largely unknown. In this study, we found that resveratrol treatment could induce cell apoptosis in murine 3T3-L1 adipocytes. Furthermore, resveratrol activated the mitochondrial apoptotic signaling pathway with the decrease in the mitochondrial membrane potential (MMP), and the activation of caspase 3. Mechanistically, we found that phosphorylation level of AMP-activated protein kinase α (AMPKα) was elevated, accompany with reduced level of phosphorylation of protein kinase B (AKT) when cells were exposed to resveratrol. By using small interfering RNAs of AMPKα and specific inhibitor for p-AKT, it was shown that activation of AMPKα could inhibit downstream of p-AKT, consequently activating mitochondrion-mediated apoptotic pathway. Additionally, we observed similar pro-apoptotic effects of Res on mouse primary adipocytes. Our findings clarified the apoptotic effects and underlying mechanisms of resveratrol in adipocytes, suggesting its potential therapeutic application in the treatment or prevention of obesity and related metabolic symptoms.