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Hutchinson-Gilford progeria syndrome (HGPS or progeria) is typically caused by a dominant-negative Câ¢G-to-Tâ¢A mutation (c.1824 C>T; p.G608G) in LMNA, the gene that encodes nuclear lamin A. This mutation causes RNA mis-splicing that produces progerin, a toxic protein that induces rapid ageing and shortens the lifespan of children with progeria to approximately 14 years1-4. Adenine base editors (ABEs) convert targeted Aâ¢T base pairs to Gâ¢C base pairs with minimal by-products and without requiring double-strand DNA breaks or donor DNA templates5,6. Here we describe the use of an ABE to directly correct the pathogenic HGPS mutation in cultured fibroblasts derived from children with progeria and in a mouse model of HGPS. Lentiviral delivery of the ABE to fibroblasts from children with HGPS resulted in 87-91% correction of the pathogenic allele, mitigation of RNA mis-splicing, reduced levels of progerin and correction of nuclear abnormalities. Unbiased off-target DNA and RNA editing analysis did not detect off-target editing in treated patient-derived fibroblasts. In transgenic mice that are homozygous for the human LMNA c.1824 C>T allele, a single retro-orbital injection of adeno-associated virus 9 (AAV9) encoding the ABE resulted in substantial, durable correction of the pathogenic mutation (around 20-60% across various organs six months after injection), restoration of normal RNA splicing and reduction of progerin protein levels. In vivo base editing rescued the vascular pathology of the mice, preserving vascular smooth muscle cell counts and preventing adventitial fibrosis. A single injection of ABE-expressing AAV9 at postnatal day 14 improved vitality and greatly extended the median lifespan of the mice from 215 to 510 days. These findings demonstrate the potential of in vivo base editing as a possible treatment for HGPS and other genetic diseases by directly correcting their root cause.
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Adenina/metabolismo , Edição de Genes/métodos , Mutação , Progéria/genética , Progéria/terapia , Alelos , Processamento Alternativo , Animais , Aorta/patologia , Pareamento de Bases , Criança , DNA/genética , Modelos Animais de Doenças , Feminino , Fibroblastos/metabolismo , Humanos , Lamina Tipo A/química , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Longevidade , Masculino , Camundongos , Camundongos Transgênicos , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Progéria/patologia , RNA/genéticaRESUMO
This study demonstrates a simple and fast method to integrate superhydrophobicity, UV protection, and photothermal effect onto PET fabrics. The surface of PET fabric forms a hierarchical rough structure through in situ oxidative polymerization of the pyrrole (Py). The 1,4-conjugate addition reaction between pentaerythritol tetraacrylate, 3-aminopropyltriethoxysilane, and octadecyl acrylate not only endows the PET fabric with superhydrophobicity but also forms a cross-linked network structure which improves the stability of multifunctional coatings on the surface of the PET fabric. In addition, the wettability of the prepared PET fabric is investigated by adjusting the Py monomer and octadecyl acrylate concentration. The results reveal that the prepared PET fabrics exhibit obviously superhydrophobic behavior with a contact angle of 155.8°. The surface temperature of the superhydrophobic PPy/PET fabric can rise to 91 °C under a simulated sunlight which is much higher than the pristine PET fabric, while reaching basically the same steady-state in five heating/cooling cycles. The prepared PET fabric also possesses excellent self-cleaning, UV shielding, and solar light absorption performances. Furthermore, the superhydrophobic PET fabric exhibited excellent stability against 180 °C high temperature, strong UV radiation, different pH solutions and organic solvent erosion, 8 h washing tests, and 25 sandpaper abrasion cycles. These findings provide a path for the future development of multifunctional fabrics using fluorine-free environmentally friendly materials.
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In recent years, photothermal materials that can convert light into heat energy have attracted extensive attention. In this work, we report a simple and effective approach to construct a self-cleaning photothermal superamphiphobic fabric. Dopamine (DA) can self-polymerize into polydopamine (PDA) and adhere to the surface of cotton fabric as a secondary reaction platform. Then, SiO2 nanoparticles were in situ grown on the PDA@fabric surface by the sol-gel method. The PDA clusters can not only provide good photothermal conversion performance but also be integrated with SiO2 to create micro-nano rough structures. Finally, the surface of SiO2 was modified by the long chain of fluorosilane to decrease the fabric surface energy, resulting in superamphiphobicity. The contact angles of water, ethylene glycol, and pump oil on the modified fabric surface could reach 161.1, 158.1, and 142.2°, respectively, making the fabric resistant to contamination by water, common beverages, and oil. Due to the adhesion of the PDA layer, the strong binding force between the fabric and SiO2 particles enabled the modified fabric to withstand various chemical and mechanical attacks, showing excellent mechanical robustness and harsh environmental stability. More importantly, the surface temperature of the modified fabric could be increased from 19.6 to 37.0 °C, which is close to the human body temperature, under the irradiation of simulated sunlight (I = 15 A, 300 s). The photothermal superamphiphobic fabrics with self-cleaning properties show great promise in the photothermal conversion field.
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Polímeros , Dióxido de Silício , Humanos , Indóis/química , Polímeros/química , Dióxido de Silício/química , ÁguaRESUMO
Telomerase is an enzymatic ribonucleoprotein complex that acts as a reverse transcriptase in the elongation of telomeres. Telomerase activity is well documented in embryonic stem cells and the vast majority of tumor cells, but its role in somatic cells remains to be understood. Here, we report an unexpected function of telomerase during cellular senescence and tumorigenesis. We crossed Tert heterozygous knockout mice (mTert+/- ) for 26 generations, during which time there was progressive shortening of telomeres, and obtained primary skin fibroblasts from mTert+/+ and mTert-/- progeny of the 26th cross. As a consequence of insufficient telomerase activities in prior generations, both mTert+/+ and mTert-/- fibroblasts showed comparable and extremely short telomere length. However, mTert-/- cells approached cellular senescence faster and exhibited a significantly higher rate of malignant transformation than mTert+/+ cells. Furthermore, an evident up-regulation of telomerase reverse-transcriptase (TERT) expression was detected in mTert+/+ cells at the presenescence stage. Moreover, removal or down-regulation of TERT expression in mTert+/+ and human primary fibroblast cells via CRISPR/Cas9 or shRNA recapitulated mTert-/- phenotypes of accelerated senescence and transformation, and overexpression of TERT in mTert-/- cells rescued these phenotypes. Taking these data together, this study suggests that TERT has a previously underappreciated, protective role in buffering senescence stresses due to short, dysfunctional telomeres, and preventing malignant transformation.
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Transformação Celular Neoplásica/genética , Senescência Celular/genética , Telomerase/genética , Telomerase/metabolismo , Animais , Ciclo Celular/genética , Células Cultivadas , Fibroblastos/patologia , Expressão Gênica , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Telômero/patologiaRESUMO
Hutchinson-Gilford progeria syndrome (HGPS) is a detrimental premature aging disease caused by a point mutation in the human LMNA gene. This mutation results in the abnormal accumulation of a truncated pre-lamin A protein called progerin. Among the drastically accelerated signs of aging in HGPS patients, severe skin phenotypes such as alopecia and sclerotic skins always develop with the disease progression. Here, we studied the HGPS molecular mechanisms focusing on early skin development by differentiating patient-derived induced pluripotent stem cells (iPSCs) to a keratinocyte lineage. Interestingly, HGPS iPSCs showed an accelerated commitment to the keratinocyte lineage than the normal control. To study potential signaling pathways that accelerated skin development in HGPS, we investigated the WNT pathway components during HGPS iPSCs-keratinocytes induction. Surprisingly, despite the unaffected ß-catenin activity, the expression of a critical WNT transcription factor LEF1 was diminished from an early stage in HGPS iPSCs-keratinocytes differentiation. A chromatin immunoprecipitation (ChIP) experiment further revealed strong bindings of LEF1 to the early-stage epithelial developmental markers K8 and K18 and that the LEF1 silencing by siRNA down-regulates the K8/K18 transcription. During the iPSCs-keratinocytes differentiation, correction of HGPS mutation by Adenine base editing (ABE), while in a partial level, rescued the phenotypes for accelerated keratinocyte lineage-commitment. ABE also reduced the cell death in HGPS iPSCs-derived keratinocytes. These findings brought new insight into the molecular basis and therapeutic application for the skin abnormalities in HGPS.
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Células-Tronco Pluripotentes Induzidas , Fator 1 de Ligação ao Facilitador Linfoide , Progéria , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Queratinócitos/citologia , Queratinócitos/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Progéria/genética , Progéria/metabolismo , Via de Sinalização WntRESUMO
In this paper, we propose spatiotemporal modulation projection lithography (STPL) technology, which is a spatiotemporal modulation technology applied to the conventional digital micromirror device (DMD) projection lithography system. Through coordinating the micro-movement of the piezoelectric stage, the flexible pattern generation of DMD, and the exposure time, the proposed STPL enables us to fabricate a microstructure with smooth edges, accurate linewidth, and accurate line position. Further application on fabricating a diffraction lens has been implemented. The edge sawtooth of the Fresnel zone plate fabricated by using the STPL is reduced to 0.3 µm, the error between the actual measured linewidth and the ideal linewidth is only within ±0.1µm, and the focal length is 15 mm, which is basically consistent with the designed focal length. These results indicated that STPL can serve a significant role in the micromanufacturing field for achieving high-fidelity microdevices.
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INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of eï¬ective treatment, has risen over the past decades but without much improvement in prognosis. OBJECTIVE: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. METHODS: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. RESULTS: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. CONCLUSIONS: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.
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Antineoplásicos/farmacologia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Neovascularização Patológica/patologia , Piridinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator 3 de Transcrição/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacosRESUMO
A flexible and efficient strategy, digital micromirror devices (DMD) based multistep lithography (DMSL), is proposed to fabricate arrays of user-defined microstructures. Through the combination of dose modulation, flexible pattern generation of DMD, and high-resolution step movement of piezoelectrical stage (PZS), this method enables prototyping a board range of 2D lattices with periodic/nonperiodic spatial distribution and arbitrary shapes and the critical feature size is down to 600â nm. We further explore the use of DMSL to fabricate microlens array by combining with the thermal reflowing process. The square shape and hexagonal shape microlens with customized distribution are realized and characterized. The results indicate that the proposed DMSL can be a significant role in the microfabrication techniques for manufacturing functional microstructures array.
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A series of novel N-phenylbenzamide-4-methylamine acridine derivatives were designed and synthesized based initially on the structure of amsacrine (m-AMSA). Molecular docking suggested that the representative compound 9a had affinity for binding DNA topoisomerase (Topo) II, which was comparable with that of m-AMSA, and furthermore that 9a could have preferential interactions with Topo I. After synthesis of 9a and analogues 9b-9f, these were all tested in vitro and the synthesized compounds displayed potent antiproliferative activity against three different cancer cell lines (K562, CCRF-CEM and U937). Among them, compounds 9b, 9c and 9d exhibiting the highest activity with IC50 value ranging from 0.82 to 0.91⯵M against CCRF-CEM cells. In addition, 9b and 9d also showed high antiproliferative activity against U937 cells, with IC50 values of 0.33 and 0.23⯵M, respectively. The pharmacological mechanistic studies of these compounds were evaluated by Topo I/II inhibition, western blot assay and cell apoptosis detection. In summary, 9b effectively inhibited the activity of Topo I/II and induced DNA damage in CCRF-CEM cells and, moreover, significantly induced cell apoptosis in a concentration-dependent manner. These observations provide new information and guidance for the structural optimization of more novel acridine derivatives.
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Apoptose/efeitos dos fármacos , DNA Topoisomerases Tipo II/efeitos dos fármacos , DNA Topoisomerases Tipo I/efeitos dos fármacos , Metilaminas/síntese química , Simulação de Acoplamento Molecular/métodos , Humanos , Metilaminas/química , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Illumination uniformity in photolithography systems determines the dimensional difference across the entire lithographic substrate. However, traditional lithography system relies on expensive and complex illumination system for achieving uniform illumination. In this paper, we propose a simple and cost-effective method based on the modulation of digital micromirror device to improve illumination uniformity. The modulation according to a digital mask achieved via an iteration program improves the uniformity to be above 95%. We demonstrate the effectiveness of the method by experimentally fabricating a linear grating. By implementing this method, the maximum dimensional difference is decreased from 3.3µm to 0.3µm. Further simulations indicate that higher uniformity is achievable once the field of view on the DMD is divided into smaller subregions.
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Hutchinson-Gilford progeria syndrome (HGPS) is a severe human premature aging disorder caused by a lamin A mutant named progerin. Death occurs at a mean age of 13 y from cardiovascular problems. Previous studies revealed loss of vascular smooth muscle cells (SMCs) in the media of large arteries in a patient with HGPS and two mouse models, suggesting a causal connection between the SMC loss and cardiovascular malfunction. However, the mechanisms of how progerin leads to massive SMC loss are unknown. In this study, using SMCs differentiated from HGPS induced pluripotent stem cells, we show that HGPS SMCs exhibit a profound proliferative defect, which is primarily caused by caspase-independent cell death. Importantly, progerin accumulation stimulates a powerful suppression of PARP1 and consequently triggers an activation of the error-prone nonhomologous end joining response. As a result, most HGPS SMCs exhibit prolonged mitosis and die of mitotic catastrophe. This study demonstrates a critical role of PARP1 in mediating SMC loss in patients with HGPS and elucidates a molecular pathway underlying the progressive SMC loss in progeria.
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Envelhecimento/fisiologia , Morte Celular/fisiologia , Miócitos de Músculo Liso/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Progéria/patologia , Diferenciação Celular/fisiologia , Sobrevivência Celular/fisiologia , Regulação para Baixo/fisiologia , Fibroblastos/citologia , Fase G2/fisiologia , Humanos , Miócitos de Músculo Liso/metabolismo , Células-Tronco Pluripotentes/citologia , Poli(ADP-Ribose) Polimerase-1 , Cultura Primária de Células , Progéria/metabolismo , Fase S/fisiologia , Pele/citologiaRESUMO
This study aimed to evaluate extensive cranioplasty involving the frontal, parietal, occipital, and temporal bones without removing the floating bone flaps in the treatment of sagittal synostosis. Sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. Patients were followed up 1-5 years. Skull growth was excellent in all patients, the anteroposterior diameter was shortened, the transverse diameter was increased, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis. Surgery without removing bone flaps is less traumatic and results in no massive bleeding. It can effectively relieve brain compression and promotes transversal expansion of the brain during surgery and subsequent normal brain development. The skull of young children is relatively thin and early surgery can easily achieve satisfactory bone reshaping. Our surgical technique is not only safe and effective but also can avoid subsequent psychological disorders caused by skull deformity.
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Transplante Ósseo/métodos , Suturas Cranianas/cirurgia , Craniossinostoses/cirurgia , Craniotomia/métodos , Dura-Máter/cirurgia , Crânio/transplante , Retalhos Cirúrgicos , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
Here, on the basis of mimotope of small analytes, we demonstrated a new approach for development of sensitive and environmentally friendly immunoassay for toxic small analytes based on the peptide-MBP fusion protein. In this work, using mycotoxin fumonisin B1 (FB1) as a model hapten, phage displayed peptide (mimotope) that binds to the anti-FB1 antibody were selected by biopanning from a 12-mer peptide library. The DNA coding for the sequence of peptide was cloned into Escherichia coli ER2738 as a fusion protein with a maltose binding protein (MBP). The prepared peptide-MBP fusion protein are "clonable" homogeneous and FB1-free products and can be used as a coating antigen in the immunoassay. The half inhibition concentration of the quantitative immunoassay setup with fusion protein (F1-MBP and F15-MBP) was 2.15 ± 0.13 ng/mL and 1.26 ± 0.08 ng/mL, respectively. The fusion protein (F1-MBP) was also used to develop a qualitative Elispot assay with a cutoff level of 2.5 ng/mL, which was 10-fold more sensitive than that measured for chemically synthesized FB1-BSA conjugates based Elispot immunoassay. The peptide-MBP fusion protein not only can be prepared reproducibly as homogeneous and FB1-free products in a large-scale but also can contribute to the development of a highly sensitive immunoassay for analyzing FB1. Furthermore, the novel concept might provide potential applications to a general method for the immunoassay of various toxic small molecules.
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Fumonisinas/análise , Imunoensaio/métodos , Proteínas Ligantes de Maltose/química , Micotoxinas/análise , Peptídeos/química , Sequência de Aminoácidos , Ração Animal/análise , Ração Animal/microbiologia , Clonagem Molecular , Escherichia coli/genética , Limite de Detecção , Proteínas Ligantes de Maltose/genética , Oryza/química , Oryza/microbiologia , Biblioteca de Peptídeos , Peptídeos/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Zea mays/química , Zea mays/microbiologiaRESUMO
BACKGROUND: An estimated 1.28 billion adults aged 30-79 years worldwide have hypertension, most (two-thirds) living in low- and middle-income countries. Pharmachological approaches have side effect, prompting exploration of Non-pharmacological approaches, like Tai Chi. Although early evidence suggests a potential favourable benefit with Tai Chi, it remains unclear whether the method can significantly reduced SBP and DBP. We aimed to assess by a systematic review and meta-analysis the effectiveness of Tai Chi in alleviating SBP and DBP on hypertension patients. METHODS: Our study adhered to the PRISMA method and was registered in PROSPERO under the code CRD42024496192. The search was carried out in the PubMed, Web of Science, Embase, and the Cochrane Library databases in December 2023. Five randomized controlled trials were included (a total of 568 patients). Risk of bias was employed to assess the quality of individual studies, and a random-effects model was utilized to examine the overall effect. RESULTS: The results showed that Tai Chi, when compared to routine care, had a statistically significant impact on SBP ((MD = 5.49, 95 % CI: 3.44 to 7.54, p = 0.001), with a heterogeneity I2 = 54%. Tai Chi did not show a significant difference in terms of DBP when compared to standard care (MD =3.18, 95 % CI: 1.89 to -4.48, p = 0.31). The included trials exhibited small sample sizes, substantial heterogeneity. CONCLUSIONS: Tai Chi effectively lowers SBP levels in hypertension patients, however, did not show a statistically significant difference on DBP.
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Pressão Sanguínea , Hipertensão , Tai Chi Chuan , Humanos , Pressão Sanguínea/fisiologia , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
PURPOSE: To investigate the effects of transcranial direct-current stimulation (tDCS) applied over the primary motor cortex (M1) and cerebellum on balance control and shooting accuracy in elite ice hockey players. METHODS: Twenty-one elite ice hockey players underwent anodal tDCS over the M1 (a-tDCSM1), anodal tDCS over the cerebellum (a-tDCSCB), concurrent dual-site anodal tDCS over the M1 and the cerebellum (a-tDCSM1+CB), and sham stimulation (tDCSSHAM). Before and after receiving tDCS (2 mA for 15 min), participants completed an ice hockey shooting-accuracy test, Pro-Kin balance test (includes stance test and proprioceptive assessment), and Y-balance test in randomized order. RESULTS: For static balance performance, the ellipse area in the 2-legged stance with eyes open and the 1-legged stance with the dominant leg significantly improved following a-tDCSM1, a-tDCSCB, and concurrent dual-site a-tDCSM1+CB, compared with tDCSSHAM (all P < .05, Cohen d = 0.64-1.06). In dynamic balance performance, the average trace error of the proprioceptive assessment and the composite score of the Y-balance test with the dominant leg significantly improved following a-tDCSM1 and concurrent dual-site a-tDCSM1+CB (all P < .05, Cohen d = 0.77-1.00). For the ice hockey shooting-accuracy test, shooting-accuracy while standing on the unstable platform significantly increased following a-tDCSM1 (P = .010, Cohen d = 0.81) and a-tDCSCB (P = .010, Cohen d = 0.92) compared with tDCSSHAM. CONCLUSION: tDCS could potentially be a valuable tool in enhancing static and dynamic balance and shooting accuracy on unstable platforms in elite ice hockey players.
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Desempenho Atlético , Cerebelo , Hóquei , Córtex Motor , Equilíbrio Postural , Estimulação Transcraniana por Corrente Contínua , Humanos , Hóquei/fisiologia , Equilíbrio Postural/fisiologia , Córtex Motor/fisiologia , Cerebelo/fisiologia , Adulto Jovem , Masculino , Desempenho Atlético/fisiologia , AdultoRESUMO
BACKGROUND: Sanniang Bay (SNB) and Dafeng River (DFR), located in the northern Beibu Gulf, is well-known as one of the eight habitats for humpback dolphins in China. This region is representative of typical estuarine and bay ecosystems and produce complex hydrodynamic seawater conditions. Moreover, anthropogenic pressure, such as eutrophication and large-scale infrastructure projects, have caused ongoing habitat deterioration and loss. It is urgent to know the phytoplankton community and their relationships with environmental factors in this region. RESULTS: In this study, we assessed the diversity and assembly mechanisms of phytoplankton communities, as well as their relationship with the physicochemical characteristics of seawater in SNB and DFR region using 18 S rDNA metabarcoding analysis. The results showed that seasonal changes markedly impacted the alpha diversity of the phytoplankton community. From March to July, with the average temperature increasing from 25.2â to 28.1â,the Shannon or Species Richness were negatively correlated with temperature. During hot season (in Sep, average temperature 32.1â), phytoplankton diversity was negatively correlated with nutrients (NH4â+, NO3-, PO43-, TN). Additionally, during the rainy season, the Bray-Curtis similarity of the phytoplankton community was significantly lower than during the dry season. In March, the distance among the sampling sites was most strongly and positively correlated with the Bray-Curtis dissimilarity. Stochastic processes, specifically dispersal limitation and ecological drift, are the primary drivers of community assembly, while deterministic assembly processes (mainly heterogeneous selection) contribute a relatively minor portion (< 17%). CONCLUSIONS: Rising temperature diminished the diversity of phytoplankton in SNB and DFR, and nutrient inputs and eutrophication in estuarine areas will aggravate the loss of phytoplankton diversity.
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Código de Barras de DNA Taxonômico , Fitoplâncton , Rios , Temperatura , Fitoplâncton/genética , China , Código de Barras de DNA Taxonômico/métodos , RNA Ribossômico 18S/genética , RNA Ribossômico 18S/análise , Biodiversidade , Estações do Ano , DNA Ribossômico/genética , Água do MarRESUMO
OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.
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Cymbopogon , Óleos Voláteis , Óleos Voláteis/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Cymbopogon/química , Cymbopogon/metabolismo , Isoproterenol , Miócitos Cardíacos/metabolismo , Fosforilação Oxidativa , RNA Mensageiro/metabolismo , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/metabolismoRESUMO
Pollen morphology of 26 taxa of Clerodendrum, as well as one species of Volkameria from China, was investigated through a scanning electron microscope (SEM). Pollen grains of Clerodendrum are monads, radiosymmetric and tricolpate, with medium or large size. The equatorial view of the pollen grains is spheroidal or subprolate and the polar view is (sub) circular or rounded triangular. The colpus membrane of the investigated taxa is sunken (rarely even). Five varying pollen types are delimited on the basis of exine sculpturing: (1) spine-tectum perforatum; (2) spine-tectum imperforatum; (3) microspine-tectum perforatum; (4) microspine-tectum imperforatum; and (5) obtuser spine. The results indicate that Clerodendrum is closely related to several genera in Lamiaceae, including Aegiphila, Amasonia, Kalaharia, Tetraclea, Volkameria, Oxera, Faradaya, and Hosea, as supported by previous phylogenic studies. Additionally, the conventional infrageneric classification of Clerodendrum based on inflorescence and leaf characters is not supported by the results. However, the palynological data can be used to identify some closely related species with similar external characteristics. In conclusion, the investigation of pollen morphology not only contributes novel data from palynology for Clerodendrum but also provides a basis for future comprehensive classification of this genus.
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Here, a facile method is reported to prepare multifunctional cotton fabrics with high flame retardancy, high electrical conductivity, superamphiphobicity, and high electromagnetic shielding. The cotton fabric surface was first modified with phytic acid (PA), which promoted dehydration and carbonization of cellulose to increase flame retardancy in the process of pyrolysis. Tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) coating with nanospheres as interlayers created hierarchical roughness that facilitated the construction of superamphiphobic surfaces and provided adhesion sites for silver nanoparticles. In addition, the TA-APTES coating improved flame retardancy because the APTES-containing silicon could form silicon carbon layers to isolate heat and oxygen. Subsequently, the surface energy of the composite cotton fabric was reduced by fluorine-containing molecules. The prepared composite cotton fabric exhibited excellent superamphiphobicity with contact angles of 160.3 and 152° for water and olive oil, respectively. The conductivity and EMI shielding efficiency of the prepared composite cotton fabric reached 629.93 S/cm and 76 dB, respectively. Importantly, the composite cotton fabric maintained a relatively stable EMI shielding efficiency even after cyclic bending and abrasion tests. Moreover, the composite cotton fabric possessed a high limiting oxygen index (LOI) of 45.3% and self-extinguishing properties with the peak heat release rate (PHHR) and total heat release (THR) reduced by 73 and 67%, respectively, than the pure cotton fabric, indicating the outstanding flame retardancy.
RESUMO
Ralstonia solanacearum is a widespread plant bacterial pathogen that can launch a range of type III effectors (T3Es) to cause disease. In this study, we isolate a pathogenic R. solanacearum strain named P380 from tomato rhizosphere. Five out of 12 core T3Es of strain P380 are introduced into Pseudomonas syringae DC3000D36E separately to determine their functions in interacting with plants. DC3000D36E that harbors each effector suppresses FliC-triggered Pti5 and ACRE31 expression, ROS burst, and callose deposition. RipAE, RipU, and RipW elicit cell death as well as upregulate the MAPK cascades in Nicotiana benthamiana. The derivatives RipC1ΔDXDX(T/V) and RipWΔDKXXQ but not RipAEK310R fail to suppress ROS burst. Moreover, RipAEK310R and RipWΔDKXXQ retain the cell death elicitation ability. RipAE and RipW are associated with salicylic acid and jasmonic acid pathways, respectively. RipAE and RipAQ significantly promote the propagation of DC3000D36E in plants. The five core T3Es localize in diverse subcellular organelles of nucleus, plasma membrane, endoplasmic reticulum, and Golgi network. The suppressor of G2 allele of Skp1 is required for RipAE but not RipU-triggered cell death in N. benthamiana. These results indicate that the core T3Es in R. solanacearum play diverse roles in plant-pathogen interactions.